EP3204111B1 - Implantable assembly - Google Patents

Description

Technical area

The invention relates to an implantable device for the location-selective detection of neuronal electrical signals that propagate along at least one nerve fiber contained in a nerve fiber bundle, as well as for the selective electrical stimulation of the at least one nerve fiber. The implantable arrangement comprises an implantable electrode arrangement, which can be placed around a nerve fiber bundle in a sleeve-like manner, with which electrical fibers selected within the nerve fiber bundle can be acted upon by nerve fibers. The electrical stimulation takes place in particular for the targeted influencing of the blood pressure in an animal or human patient.

State of the art

Arterial hypertension is a common, common lifestyle disease that threatens the lives of millions of patients and at the same time severely affects health systems. Previously known therapeutic measures are based on the administration of antihypertensive drugs, such as. ACE inhibitors, beta-blockers, etc., but these have in addition to the desired antihypertensive effect considerable side effects, such as bradycardia, heart failure, asthma attacks, etc. on. In addition, despite the development of new antihypertensive drugs in up to 30% of all patients with appropriate medication no adequate target blood pressure can be achieved, see article by HR Black, et al., "Principal results of the controlled onset Verapamil investigation of cardiovascular end points (Convince), TRIAL. Jama, 289 (16), pp. 2073-2082), 2003 ,

Another therapeutic approach to the encounter of hypertension pursued by a study by the applicant, in the article of Dennis TT Plachta, Oscar Cota, Thomas Stieglitz, Mortimer Gierthmuehlen, "Selective Discharge and Stimulation for a Hypertensive Implant Using Multichannel Cuff Electrodes", tm - Technisches Messen, 2013, Vol.80 (5), pp.163- 172 has been published. The findings obtained on the basis of animal experiments carried out on rats establish the possibility of detecting neuronal electrical signals spatially resolved from the nerve fiber bundle section by means of an electrode arrangement implanted on a nerve fiber bundle section of the vagus nerve and applying electrical signals to selected nerve fibers to stimulate them for the purpose of technically initiated blood pressure reduction. Such a vagus nerve stimulation thus basically has the potential to be established as an alternative to the treatment of refractory blood pressure.

The concept of selective vagus nerve stimulation is based on the experience of many years of established and established neuromodulatory therapy of severe forms of epilepsy, in which the vagus nerve is electrically stimulated with the help of an implanted electrode assembly to at least their extent in terms of strength in epileptic seizures and to mitigate their duration, see F. Sidiqui, et al., "Cumulative Effect of Vagic Nerve Stimulators on Intractable Seizures Observed over a Period of 3 Years," Epilepsy and Behavior, 18 (3), pp. 299-302, 2010 such as T. Stieglitz, "Neuroprosthetics and Neuromodulation - Research Approaches and Clinical Practice in Therapy and Rehabilitation", Bundesgesundheitsblatt - Health Research - Health Protection, 53 (8), pp. 783 - 790, 2010 ,

In contrast, for the chronic treatment of hypertension, the blood pressure-relevant fibers must first be measured by localizing them subsequently suitably selectively electrically stimulated. In order to protect the vagus nerve as much as possible by the implantation of the application of an electrode arrangement and as far as possible not to irritate the epineurium of the vagus nerve, in the cited paper by Dennis TT Plachta et al. proposed the use of a so-called. Cuff electrode which is extraneurally attachable to the vagus nerve. This has the advantage of a relatively easy positioning of the cuff electrode along the vagus nerve and also allows a slightly invasive and therefore gentle and easy to perform surgical intervention on the patient.

For natural blood pressure control is the Baroreflex, which represents a homeostatic, self-regulating mechanism and activates reflectorically different effectors with an increased blood pressure. Among other things, the heart rate is lowered, but also the arterial vessels are widened in order to lower the blood pressure. In the case of low blood pressure, the baroreflex is suppressed, increasing heart rate and narrowing blood vessels to increase blood pressure. The sensory inputs for the baroreflex represent so-called baroreceptors, which are located, inter alia, in the walls of the aortic arch. From there, the blood pressure information draw monosynaptically along the blood pressure-relevant nerve fibers, hereinafter referred to as baroreceptive fibers, in the brainstem. When a blood pressure threshold is exceeded, the baroreflex induces an inhibition of sympathetic nerve fibers, resulting in an immediate lowering of blood pressure. With the help of referring to FIGS. 2a, b It is possible to use this baroreflex mechanism by selectively detecting and also "overwriting" the pressure information supplied to the brain stem so as to substantially increase the brainstem in this way To suggest a blood pressure lowering, which initiates a natural significant lowering of blood pressure.

FIG. 2a shows the known sleeve electrode E in a planar plan view in a planar unfolded state. FIG. 2b shows the cuff electrode E in the implanted state in which areas B1, B2 of the cuff electrode E are folded on each other for a space-saving form and moreover a carrier substrate area 1B of the cuff electrode E provided with a first electrode arrangement 2 comprises a region of a nerve fiber bundle NFB.

The sleeve electrode E consists of a flexible, biocompatible carrier substrate 1, which is in the realized embodiment, an approximately 11 micron thick polyimide film, at whose the plane in FIG. 2a facing carrier substrate top side for the purpose of spatially resolved detection of neuronal electrical signals as well as for the selective electrical stimulation of individual in the nerve fiber bundle NFB extending nerve fibers NF a composed of a plurality of individual electrodes first electrode assembly 2 is applied. The individual electrodes of the first electrode arrangement 2 come into direct surface contact with the epineurium EPI of the nerve fiber bundle NFB, since the carrier substrate 1 unrolls itself in the carrier substrate region 1B by corresponding impressing of a mechanical foil prestress to form a straight-cylindrical carrier substrate surface 1 'oriented toward the nerve fiber bundle NFB, as this in FIG. 2b is apparent. Thus, the individual electrodes of the first electrode arrangement 2 assume an annular space shape bent in the circumferential direction U around the nerve fiber bundle NFB.

Both for location-selective detection of neuronal electrical signals as well as for the selective electrical stimulation of at least one nerve fiber NF serve three axially equally spaced from each other arranged first electrode structures 3, in the circumferential direction U at least two, in the illustrated embodiment according to FIG. 2a, b each eight first electrode surfaces 4 include. The respective eight first electrode surfaces 4 belonging to a first electrode structure 3 are equally distributed in the circumferential direction U, ie arranged at 45 ° angular intervals. This allows an eightfold, in the circumferential direction divided site selectivity for the location-selective detection of neuronal electrical signals from the nerve fiber bundle NFB to be examined. The first electrode strips 5 which are arranged axially on both sides next to the three first electrode structures 3 and which completely surround the nerve fiber bundle NFB, serve as ground potential in the case of the locally selective detection of neuronal electrical signals; If, on the other hand, it is intended to electrically stimulate selectively selected nerve fibers NF within the nerve fiber bundle NFB, these first electrode strips 5 each serve as anode or as opposite polarity.

The triple or tripole arrangement of the respective first electrode structures 3, via whose respective first electrode surfaces 4 monopolar neuronal electrical signals detected or electrical signals can be delivered for the purpose of site-selective stimulation allows to detect impedance changes due to tissue growth on the metallic electrode surfaces 4 On the other hand, blood pressure-relevant neuronal signals which run axially along a corresponding nerve fiber NF with a slight time offset through the tripole arrangement can be detected by means of suitable tripolar amplification. In addition to the above-described first electrode structures 3 and first, each taking a ring shape accepting electrode strips 5, all of which at the in FIG. 2a On the back of the carrier substrate 1, a second electrode arrangement in the form of reference electrodes 12, which serve for detecting the intracorporeal electrical background mass signal or Rauschniveaus, located on the back of the carrier substrate 1 is located on the back of the support substrate 1 On the other hand, open up the possibility to detect ECG signals using the sleeve electrode E. The electrode assembly which can be implanted as a sleeve electrode E can be connected via the electrical connection structures V to a hermetically sealed signal detector and generator 6, which is likewise designed as an implant.

With the known implantable electrode arrangement could be shown in animal experiments on rats that with the help of equally distributed around the nerve fiber bundle NFB tripolar arranged a total of 24 first electrode surfaces blood pressure correlated, neuronal electrical time signals, hereinafter referred to as baroreceptive signals, can be detected moreover, with respect to their circumferentially dependent signal levels to locate the baroreceptive nerve fibers. The stimulation was tripolar in each case with that electrode surface 4 or those electrode surfaces 4 of the centrally arranged first electrode structure 3 of the tripole arrangement, was detected by the detection of the respective largest signal level among the barorezeptiven signals. It could be shown that by selective stimulation of baroreceptive nerve fibers, the blood pressure can be reliably reduced significantly, with only a very weak bradycardia (pulse reduction below 60 beats per minute) and a barely significant bradypnea (reduction of breathing under 20 breaths per minute) occurred ,

For selective electrical stimulation of the baroreceptive nerve fibers, electrical stimulation signals were applied to the respectively selected electrode surfaces 4 of the centrally arranged electrode structure on the basis of a specific combination of fixed stimulation parameters. In this case, the stimulation signals in the form of electrical stimulation events were applied to the selected nerve fibers at freely selectable intervals, for example. An electrical stimulus composed of 100 individual pulses was applied to the nerve fiber bundle via the respectively selected electrode surface (s) every 20 seconds. Each individual pulse had a stimulation pulse duration of 0.6 ms with an anodic and cathodal stimulation amplitude of 0.8 mA each, which allows electrode polarization. With a repetition rate of the individual pulses, the so-called stimulation frequency, of 40 Hz, the total duration of a single electrical stimulus was 100 × 25 ms, thus 2.5 seconds. In the stimulation experiments performed on rats different fixed stimulation parameters were used. namely a stimulation frequency of 30 to 50 Hz, a stimulation pulse duration of 0.1 ms to 0.5 ms and a stimulation amplitude of 0.3 mA to 1.5 mA.

Although the findings obtained in the context of previous animal experiments with regard to influencing the blood pressure by selective electrical stimulation of baroreceptive nerve fibers appear promising, at least the quantitative relationships between the electrical stimulation event and the biological response in the form of an on the basis of organic regulatory mechanisms initiated blood pressure reduction still largely understood. Particularly in the case of larger animals than the rats hitherto used in animal experiments, or even in humans, it is necessary to carry out regulative stimulations with a greater degree of predetermination, the organically induced regulation result of which should come within a quantitatively determined tolerance range.

Presentation of the invention

The object of the invention is to develop an implantable arrangement for the location-selective detection of neuronal electrical signals propagating along at least one nerve fiber contained in a nerve fiber bundle, as well as for the selective electrical stimulation of at least one nerve fiber with an electrode arrangement as described above, so that the stimulative influence on certain areas of the autonomic nervous system, in particular on the vagus nerve for purposes of influencing blood pressure with a significantly greater precision can be made. If appropriate regulatory measures are to be applied to larger organisms than rats, especially humans, it must be ensured that the desired neuronal, physiological and / or organic condition sets in at least within a foreseeable quantifiable tolerance range. All necessary measures should also exclude unwanted biological side effects. Basically, the arrangement should be next to the desired Be able to influence blood pressure alternatively or in combination also for any other vegetative but also sensorimotor state variables for the purpose of a purposeful influence.

The solution of the problem underlying the invention is specified in claim 1. The idea of solution in advantageous wise further developing features are the subject matter of the subclaims and the further description with reference to the exemplary embodiments.

In contrast to the above-described procedure for the electrical stimulation of at least one selected nerve fiber, each with rigidly predetermined stimulation parameters, i. Stimulation pulse duration, stimulation amplitude and stimulation frequency, the implantable arrangement according to the solution allows the generation of electrical stimulation signals in their shape, d. H. the temporal amplitude curve, the pulse waveform of natural blood pressure signals are largely aligned and applied in temporal overlap with the natural blood pressure signals to the baroreceptive nerve fibers, so that along the baroreceptive nerve fibers from the baroreceptors to the brain stem transmitted, natural blood pressure signals are literally overwritten. Thus, the stimulation according to the solution is not carried out, as hitherto, from a pulsatile "on-off-on-off" scheme, but the technical, electrical stimulation signals applied along the baroreceptive nerve fibers are fed to the brainstem with a stimulation frequency adapted to the natural signal rhythm, i , H. each in those natural time windows where the brainstem awaits the natural blood pressure signals.

The natural form of a pulse wave passing through the barenotonic fields in the aortic arch typically has a pulse duration of less than one second and is further characterized by a strong, fast and non-linear pulse wave rise followed by a slow, also non-linear decay. This mechanical pulse wave is generated by the baroreceptors in a neuronal, electrical signal transduced. This neuronal electrical signal is directed to the brain stem via the vagus and contains the information regarding the strength and duration of the mechanical pulse wave. In adaptation to this natural neuronal electrical signal form, the technically initiated influence on the natural organic regulating mechanism is achieved by chronologically coherently overwriting the natural, neuronal, electrical time signals with technical electrical stimulation signals applied to the at least one selected baroreceptive nerve fiber. whose amplitude levels are raised or lowered with respect to the natural, neuronal, electrical time signals, depending on the desired therapeutic goal. In this way, the natural, organic blood pressure regulation mechanism is not or not significantly irritated, ie the brainstem, which receives the technically manipulated electrical stimulation signals, can not detect any difference to the natural, neuronal, electrical time signals. As a result, the natural organic control mechanism is activated, which naturally leads to a control result that is characterized by a specific, expected blood pressure value setting.

Furthermore, the implantable arrangement according to the invention offers the possibility of autonomously controlling blood pressure value monitoring, i. H. the natural organic regulatory mechanism is activated only in those cases where a significant deviation from a standard blood pressure is detected. In a further advantageous manner, it is possible to implant the device by self-control, d. H. operate in the manner of a closed-loop function, in which the organic control result caused by an electrical stimulation is detected, evaluated and, if necessary, subjected to a corresponding readjustment.

For this purpose, the implantable arrangement according to the invention is characterized for location-selective detection of neuronal electrical signals propagating along at least one nerve fiber, preferably a baroreceptive fiber, contained in a nerve fiber bundle, as well as for the selective electrical stimulation of the at least one nerve fiber by the following components:
In addition, the solution according to the invention will be explained by the example of influencing the blood pressure as a physiological parameter without limiting the general idea of the invention. Of course, the implantable device can also be used to influence other physiological parameters, such as respiratory rate, heart rate, body temperature, etc., or other conditions, for example autoimmune diseases, cardiac arrhythmia, severe depression, epilepsy, etc. The implantable device can be used for alternative therapy Use body functions also on other peripheral nerves or nerves of the central or autonomic nervous system. As an example, the area of motor neuroprostheses after central paralysis in spinal cord or brain injuries may be mentioned. In these cases, the sensory signals of the pressure and Lagerezeptoren example of the hand can be selectively recorded with implantable arrangement and the grip force can be controlled automatically according to a setpoint specification. In the field of neuromodulation, rehabilitation after stroke and hemiparesis using the implantable device can be expected. In this case, the sensory signal can be increasingly coupled in order to improve the rehabilitation success. Also conceivable is a regulated respiratory stimulator with the aid of the implantable arrangement via the phrenic nerve at the diaphragm, the modulation of the sympathetic nervous system at the limiting strand or the efficient pain therapy by highly selective peripheral nerve stimulation.

For location-selective detection of neuronal electrical signals along selected nerve fibers within a nerve fiber bundle and also for selective electrical stimulation of the at least one selected nerve fiber, an implantable electrode arrangement is provided which is applied to a biocompatible carrier substrate which can be placed around the nerve fiber bundle in a cuff-like manner, which faces the nerve fiber bundle in the implanted state oriented, straight cylindrical carrier substrate surface has. In addition, a second electrode arrangement is on the biocompatible carrier substrate arranged to detect the ECG signal representing cardiac activity. It is not necessary for the second electrode arrangement to be applied to the same carrier substrate surface of the carrier substrate as the above first electrode arrangement.

The implantable electrode assembly, i. H. at least comprising the first and second electrode arrangement, is electrically connected to an evaluation / control unit or connected to this connectable, in which the spatially selectively detected, neural, electrical signals as well as the ECG signal are evaluated time-resolved, so that a blood pressure, correlated neural time signal is derivable. The trained as a digital signal processor or microcontroller evaluation / control unit is able to process signal data and to generate control signals.

A first comparator unit connected to the evaluation / control unit serves to determine a characteristic relative time offset between the metrologically recorded ECG signal and the neuronal time signal correlated with the blood pressure.

Advantageously, in this case, the time interval between the R wave of the ECG time signal and a signal edge point is determined along the signal edge of the time signal, which correlates positively with the blood pressure wave, and is detected by measurement. The metrologically detected, neural time signal correlated with the pulse wave or the blood pressure is characterized by a mostly multi-phase signal shape which depends on the configuration of the first electrode arrangement, to which a characteristic signal edge point can be assigned, which is used to determine a time offset for the ECG time immediately ahead. Signal is used. The determined time offset between the ECG signal and the blood pressure wave or the pulse wave or the time signal correlated with the blood pressure wave is used in the following for a time exact adaptation of the generation of technical stimulation signals to along the Baroreceptive nerve fibers propagating, natural, neural electrical signals.

Furthermore, the evaluation / control unit determines a time window within which the blood pressure correlated neuronal time signals is above a certain amplitude level, i. the time window corresponds to the pulse duration of a blood pressure wave. The aim is for purposes of influencing blood pressure within this determined using the evaluation / control unit time window to the at least one selected barorezeptive nerve fiber to apply a technical, electrical stimulation signal, so that the brain, the electric stimulation signal with an adapted to the natural pulse wave duration and signal duration receives a time at which the brain receives the normal, d. H. expected natural blood pressure signals.

Furthermore, the evaluation / control unit is electrically connected to a first function generator which generates an electrical stimulation signal composed of a multiplicity of n individual pulses within the time window determined by the evaluation / control unit, which has the determined relative time offset with respect to the ECG signal. whose phase and temporal amplitude course is adapted to the phase and amplitude profile of the derived neuronal time signal correlated with the physiological parameter, preferably blood pressure. Preferably, the electrical stimulation signal differs only by the time-varying amplitude level, which in the case of hypertension therapy is greater or higher than that of the correlated with the natural blood pressure, the neuronal time signal. Thus, the brain receives the information about a greatly increased blood pressure against which appropriate natural organic regulatory mechanisms are activated.

For converting and forwarding the electrical stimulation signal composed of the plurality of n individual pulses in the form of a current signal, the first function generator as well as the first electrode arrangement of the implantable electrode arrangement are connected directly or indirectly via a first signal-current converter which generates the electrical stimulation signal for selectively conduct electrical stimulation of the at least one nerve fiber to the first electrode assembly.

With the exception of the implantable electrode assembly, the first electrode assembly in physical, d. H. electrical contact with the epineurium of the nerve fiber bundle, all other components of the implantable assembly, i. H. the evaluation / control unit, the first comparator unit, the first function generator as well as the first signal-to-current converter integrated in an implantable module, d. H. surrounded by a capsule consisting of biocompatible material in a fluid-tight manner, wherein at least one electrical connection structure is provided for electrical contacting of the components combined within the implantable module with the implantable electrode arrangement.

Due to the temporally coherent agreement of the selective electrical stimulation with the transmission of natural, neuronal electrical signals along selected baroreceptive nerve fibers, as well as the adaptation of the stimulation signals to signal duration and waveform to the natural baroreceptive neuronal signals, the difference is only reflected in one compared to the natural baroreceptive signals raised, ie higher, time-varying amplitude level again. Of course, it is also possible to apply lower amplitude levels with the aid of the implantable arrangement according to the invention to the at least one selected nerve fiber. To quantify the extent of the technical amplitude level increase or decrease, the implantable device provides at least one second comparator unit electrically connected to the evaluation / control unit, which is assigned at least one signal level associated with the neural time signal correlated to the blood pressure , compares with at least one reference signal and, as a result, generates a differential level value. The evaluation / control unit determines at least on the basis of the determined difference level value at least the temporal amplitude curve of the stimulation signal, ie deviates with the help of the implantable device Depending on the regulatory requirement, the time-varying amplitude level of the electrical stimulation signal is raised or lowered relative to the measured neuronal time signal correlated with the blood pressure, depending on the control requirement. In the case of hypertension therapy, it is usually necessary to significantly increase the time-varying amplitude level in order to supply the brain with the information about an increased blood pressure, which further attempts to reduce the excessive blood pressure level in the context of natural organic or biological control mechanisms.

The above-described electrical stimulation, which with the help of in FIG. 2 A and b illustrated cuff electrode arrangement is carried out along the baroreceptive nerve fibers with isotropic Signalrichtungseinkopplung, ie without specifying a fixed signal propagation direction, so that the electrical stimulation signals can propagate along both afferent and efferent nerve fibers. In order to suppress the signal propagation of electrical stimulation signals along efferent nerve fibers, ie towards the heart, without exerting a significantly lasting influence on non-baroceptive, afferent and efferent nerve fibers within the nerve fiber bundle, one is better than in FIG. 2 described electrode assembly modified at least one for inhibiting unidirectional electrical signal transmission along at least one selected nerve fiber within a nerve fiber bundle formed third electrode assembly.

The third electrode arrangement likewise applied to the same, integrally connected carrier substrate on the same carrier substrate surface as the first electrode arrangement is spatially fixed to the first electrode arrangement, in particular to the first electrode surfaces of the at least three first electrode structures, with the aid of which baroreceptive nerve fibers within the Nerve fiber bundle site selective and, moreover, are selectively electrically stimulable. With knowledge of the localized baroreceptive nerve fibers, the third electrode arrangement may be used for purposes of selectively inhibiting the baroreceptive nerve fibers to suppress transmission of electrical stimulation signals along efferent, ie nerve leading, nerve fibers. At least two, preferably four or more, second electrode surfaces of at least one third electrode structure are used for this purpose. Like the first electrode surfaces of one of the at least three first electrode structures, they are equally distributed in the circumferential direction of the carrier-fiber surface facing the nerve fiber bundle. For purposes of inhibiting localized efferent baroceptive nerve fibers, at least one of the third electrode surfaces of the third electrode structure is electrically activated, thereby providing selective, timed, selective inhibition of the respective efferent nerve fiber. In this case, an electric polarization field enters the nerve fiber bundle from the respectively at least one activated, third electrode surface and interacts primarily with the nerve fiber to be inhibited. In order to axially delimit the electric polarization field propagating into the nerve fiber bundle during the inhibition, second electrode strips axially attached on both sides to the third electrode structure serve as annular electrodes which completely surround the nerve fiber bundle in the implanted state of the cuff electrode.

For purposes of inhibiting selected efferent nerve fibers, the modified implantable electrode assembly is to be applied to the nerve fiber bundle such that the additionally provided third electrode assembly faces the heart or baroreceptive receptors, ie caudal, and the first electrode assembly selectively detects neural electrical signals as well as the electrical stimulation of localized nerve fibers is made, the brain, ie rostral, oriented along the nerve fiber bundle.

With the aid of the third electrode arrangement, the inhibition can be realized either by means of a so-called anodal block or by application of sinusoidal signals of frequencies in the kilohertz range. In the case of the anodal block, at least one of the second electrode surfaces is anodically polarized, thereby producing a voltage potential prevailing at the location of the efferent nerve fiber, by which an activating stimulation of the corresponding nerve fiber is suppressed. Likewise, an inhibition can be achieved by means of a high-frequency signal application in which a high-frequency electrical inhibition signal is applied to at least one selected third electrode surface, whereby the electrical signal transmission mechanisms along the efferent nerve fibers come to a standstill for a short time.

In both cases, the solution provided according to third electrode arrangement acts due to their spatial axial limitedness, which is given by the axial distance of the two third electrode strips, despite their proximity to the first electrode structure, after all, the implantable electrode assembly should not exceed an axial length of 4 cm, axially spaced bounded along the efferent nerve fibers to be inhibited, so that the first electrode arrangement arranged on the brain side along the nerve fiber bundle can couple in the respectively localized afferent nerve fibers to the brain leading electrical stimulation signals uninfluenced by the inhibition mechanism. In this way, any side effects due to possible direct stimulations towards the heart, i. efferent nerve fibers are excluded.

Advantageously, in the implanted state of the cuff electrode, the third electrode surfaces of the third electrode structure are equally distributed along a virtual circular line in order to selectively and effectively inhibit localized efferent nerve fibers relative to the peripheral edge of a nerve fiber bundle.

Not necessarily, however, in an advantageous form, the third electrode surfaces are identical in shape and size with each other, their axial extensions are each selected identically, as the axial extensions of the first electrode surfaces of the first three electrode structures. The circumferentially oriented extension of the respective third electrode surfaces is chosen larger than the circumferentially oriented extent of the first electrode surfaces. Thus, the third electrode surfaces preferably have a larger areal dimension than the first electrode areas, whereby the spatial selectivity with which the third electrode surfaces are able to electrically polarize certain efferent nerve fibers is less than the spatial selectivity with which the first electrode surfaces are able to electrically stimulate localized nerve fibers. Alternatively, the third electrode surfaces may be formed instead of a rectangular shape as circular areas. This has the advantage that no local, caused by edges or corners electric potential field peaks form.

The third electrode arrangement is preferably designed in the form of a tripolar electrode arrangement, i. H. the third electrode structure is delimited axially on both sides by an annular third electrode strip, wherein the axial distance between the two third electrode strips along the carrier substrate is preferably selected between 0.5 cm and 3 cm, in particular between 0.75 cm and 1.25 cm. The ring-shaped third electrode strips preferably have an axial extent of between 1 μm and 5 mm, preferably between 100 μm and 4000 μm.

The third electrode surfaces of the third electrode structure are arranged axially in the middle between the two third electrode strips and have an axial extension, so that the respective axial distance from the second electrode strips is greater than their own axial extension.

In particular, with regard to the possibility of carrying out depolarizing measures, it is conceivable instead of a third Electrode structure to arrange three axially spaced third electrode structures between the third electrode strip, as it were to form the respective first electrode structure within the first electrode assembly. For the sake of completeness, it should be mentioned that it would also be conceivable to arrange more than three first and third electrode structures between the respective first and third electrode strips. Thus, three, five, seven or more odd first and / or third electrode structures could be provided.

In a preferred exemplary embodiment, a third electrode structure comprises four third electrode surfaces, the electrode surface dimension of which is selected in each case smaller than a quarter of the surface size of a respective third electrode strip. Since the first and third electrode strips provided in both the first and in the third electrode arrangement serve as ground or opposite poles for polarizing the respectively first and third electrode structure, the surface sizes of the first and third electrode strips are each chosen to be identical for reasons of charge-symmetrical relationships , However, it is also conceivable to have an individually independent area size choice in the formation of the first and third electrode strips.

Furthermore, it has been found to be advantageous to use all the electrodes of the third electrode arrangement, i. the third electrode surfaces and third electrode strips, to be made of an electrically conductive material, which has a lower charge transfer capacity than the electrode material from which consist of the first electrode surfaces of the first electrode assembly. As a particularly suitable material with a particularly high charge transfer capacity iridium oxide is used to form the respective first electrode surfaces of the first electrode assembly, whereas the material of the third electrode surfaces and third electrode strips consists of platinum or of an electrically conductive polymer.

All electrode surfaces of both the first and third electrode arrangements are preferably flush with the carrier substrate surface of the carrier substrate formed or arranged offset against this, so that they do not project beyond the carrier substrate surface in order to produce as gentle as possible surface contact to the epineurium of the nerve fiber bundle. Due to the non-invasive surface contact, the implantable electrode arrangement can be easily applied and positioned surgically along the nerve fiber bundle, whereby the epineurium is only slightly or not irritated.

Further, to counter implant-related tissue irritation and inflammatory responses, it is desirable to provide the biocompatible polymer carrier substrate with an inflammatory response inhibiting agent at least in those areas which are in direct surface contact with the nerve fiber bundle.
A further measure for reducing mechanical irritation of the nerve fiber bundle, which may arise from the surface contact with the sleeve-like sleeve electrode, relates to a rounding of axial boundary edges of the carrier substrate surrounding the nerve fiber bundle such that the biocompatible carrier substrate in the region of the straight-cylindrical carrier substrate surface oriented axially facing the nerve fiber bundle has opposite edge regions, on which the carrier substrate has a greater substrate thickness than in the remaining carrier substrate region, wherein the edge regions have rounded edges.

In the region of the third electrode arrangement, which serves to electrically inhibit localized nerve fibers, a further preferred embodiment provides at least one, preferably a plurality of optical waveguide openings or apertures, via which light can be applied or coupled through the epineurium of the nerve fiber bundle. The optical waveguide openings are preferably arranged axially adjacent to the two second electrode strips and reproduced in shape, size and distribution corresponding to the third electrode surfaces of the third electrode structure. By providing a plurality of spatially separated optical waveguides which open on the carrier substrate surface facing the nerve fiber bundle, For example, uniform or different optical signals with different wavelengths can be applied to the nerve fiber bundle for purposes of optically activating neuronal optogenetic reactions within the nerve fiber bundle. Thus, a multiplicity of suitably arranged lightwave exit openings or apertures within the nerve fiber bundle can trigger neuronal activation or inhibition reactions in a spatially selective manner, which can be carried out alternatively or in addition to the neural processes produced via the electrode surfaces.

As already mentioned, the implantable electrode arrangement formed in accordance with the solution is to be applied along the nerve fiber bundle in such a way that the third electrode arrangement comes to rest along the nerve fiber bundle in the direction of the heart. In this way, it is ensured that efferent nerve fibers can be inhibited, whereas the first electrode arrangement oriented towards the brain along the nerve fiber bundle, for purposes of selective stimulation, localizes afferent, i. H. can be used to brain leading nerve fibers. Should there be a need to selectively inhibit afferent nerve fibers, the modified implantable electrode assembly may be implanted in the reverse orientation along the nerve fiber bundle. A further possible embodiment provides a second inhibiting third electrode arrangement, which is mounted axially next to the first electrode arrangement, opposite the third electrode arrangement.

The intracorporeal implantation of the electrode arrangement surrounding the nerve fiber bundle in a sleeve-like manner is furthermore confronted with the fundamental problem that the electrode strips and electrode surfaces applied to the polyimide carrier substrate are exposed to a continuous moist environment, whereby degradation phenomena occur, in particular at the planar connections between the electrode surfaces and the polyimide carrier substrate which can lead to local detachment and associated therewith at least to contact degradation, by which ultimately the electrical Efficiency of the electrode assembly is impaired. In a preferred embodiment, at least the first and third electrode strips each have at least one local opening in order to counteract this environment-caused detachment phenomena between the metallic electrode surfaces and the polyimide carrier substrate, wherein the first and third electrode strips are connected in a planar manner to the carrier substrate or the carrier substrate surface are such that the polymer or polyimide, which consists of the carrier substrate, at least partially penetrates the at least one opening. This creates an improved mechanical anchoring of the respective electrode strips to the carrier substrate.

A further possibility for a permanently stable connection between the electrode surfaces or electrode strips and the biocompatible polyimide or polymer material of the carrier substrate is reflected in a special embodiment of the electrode surfaces or electrode strips, as well as a possible special integration of the electrodes into the carrier substrate. For this purpose, in particular the first and third electrode strips each have a metallic base plate with a flat top and bottom, with at least one, preferably a plurality of the top of the base plate orthogonal locally superior structural elements, which are preferably formed pillar, rib, sleeves or web-like , The metallic base plate is completely enclosed by the biocompatible polymer of the carrier substrate, with the exception of a first surface region of the at least one structural element which is oriented towards the carrier substrate surface and does not project beyond it. Thus, the electrode contact surface which is freely accessible on the carrier substrate surface is reduced, but due to the hermetic enclosure of the base plate and the structural elements integrally connected thereto, with the exception of the surface regions oriented toward the carrier substrate surface, the biocompatible polymer of the carrier substrate is completely enclosed. Penetration of environment-conditioned liquid or moisture between the electrode strips and the biocompatible polymer of the carrier substrate is considerably more difficult, so that degradation phenomena largely can be excluded. In a further preferred embodiment, an adhesion promoter layer or an adhesion promoter layer arrangement is preferably introduced between the underside of the metallic base plate and the biocompatible polymer of the carrier substrate, which counteracts possible moisture-related detachment phenomena.

The implantable arrangement according to the invention advantageously makes it possible to carry out a method for the location-selective detection of neuronal electrical signals which propagate along at least one nerve fiber of a human or animal living organism contained in a nerve fiber bundle and for the selective electrical stimulation of the at least one nerve fiber. In particular, in the case of electrical stimulation of afferent nerve fibers, ie nerve fibers, along which neuronal electrical signals are directed to the brain, the electrical stimulation according to the solution causes no or no significant irritation of the brain function, especially a distinction between natural, neuronal electrical signals and electrical stimulation signals in the brain is not possible. The process according to the invention is characterized by the following process steps:
First of all, neuronal electrical signals propagating along a nerve fiber, which are to be influenced, are to be detected in a spatially selective manner. This step can be carried out with an electrode arrangement known per se. On the basis of the acquired, natural, neural electrical signals, "artificial" electrical signals are generated whose signal duration and amplitude curve correspond to the detected natural neuronal electrical signals. Depending on a therapeutic target, for example, blood pressure reduction or increase, the "artificially" generated electrical signals are modified in such a way that the amplitude is increased or decreased at least within a temporal portion of the signal duration of the electrical signals. Preferably, the temporal amplitude profile of the electrical signal is raised in total, ie uniformly raised or lowered over the entire signal duration of the electrical signal. By this measure electrical stimulation signals are obtained, which are connected to the nerve fiber in temporal phase with the neuronal electrical signals are applied. This means that the natural, neuronal electrical signals are temporally coherent, ie they are overwritten according to their temporal signal duration and temporal sequence along the nerve fiber, each with an electrical stimulation signal. By this process of temporally coherent overwriting, the information inherent in the natural neuronal electrical signal is replaced by artificially generated information impressed on the electrical stimulation signal.

Since the electrical stimulation signals propagate along the afferent nerve fiber in the same time sequence and with the same temporal signal duration as the original neuronal signals, it is not possible to distinguish between neuronal electrical signals and electrical stimulation signals in the brain.

In order to avoid that the electrical stimulation signals applied to the respective nerve fiber propagate bidirectionally along the nerve fiber, a preferred supplement provides that an electrical inhibition signal to the nerve fiber is applied in such a way before and / or during the application of an electrical stimulation signal to the nerve fiber so that the electrical stimulation signal can only propagate unidirectionally along the nerve fiber. The suppression of the signal propagation into the unwanted nerve fiber direction is preferably carried out with the aid of an additional electrode arrangement serving for the electrical application of the electrical stimulation signals, a separate electrode arrangement which is attached adjacent to the location of the application of the electrical stimulation signals along the nerve fiber and facing away from the propagation direction of the electrical stimulation signals.

All further, the implantable arrangement advantageously forming features will be explained below with reference to the figures.

Brief description of the invention

Fig. 1

Blockdiagramm zur Illustration sämtlicher Komponenten der lösungsgemäßen implantierbaren Anordnung,

Fig. 2a,b

implantierbare Elektrodenanordnung gemäß Stand der Technik,

Fig. 3.

Zeitdiagramme zur Illustration des EKG-Signals und dem mit dem Blutdruck korrelierten neuronalen Zeitsignal,

Fig. 4

Darstellung zur Erläuterung des sich aus n Einzelpulsen zusammensetzenden Stimulationssignals sowie zur Erläuterung eines Einzelpulses,

Fig. 5

Darstellung zweier alternativer Betriebsweisen der implantierbaren Anordnung zur Blutdruckregelung,

Fig. 6

Draufsicht einer schematisierten implantierbaren Elektrodenanordnung mit einer dritten Elektrodenanordnung zu Inhibition selektiver Nervenfasern,

Fig. 7a

Darstellung eines Elektrodenstreifens mit Öffnung,

Fig. 7b

detaillierte Darstellung eines in das Trägersubstrat integrierten Elektrodenstreifens,

Fig. 7c

Alternative Ausbildung eines Strukturelementes,

Fig. 8a-f

Darstellungen einer die implantierbare Elektrodenanordnung zusätzlich verstärkende Manschette,

Fig. 9

Hydraulische Applikationsstruktur der implantierbare Elektrodenanordnung, und

Fig. 10

Flußdiagramm zur Durchführung der elektrischen Stimulation einer Nervenfaser.

The invention will now be described by way of example without limitation of the general inventive idea by means of embodiments with reference to the drawings. Show it:

Fig. 1

Block diagram illustrating all components of the implantable device according to the invention,

Fig. 2a, b

implantable electrode assembly according to the prior art,

Fig. 3.

Timing diagrams illustrating the ECG signal and the blood pressure correlated neural time signal,

Fig. 4

Representation for explaining the pacing signal composed of n individual pulses and for explaining a single pulse,

Fig. 5

Representation of two alternative modes of operation of the implantable arrangement for blood pressure regulation,

Fig. 6

Top view of a schematized implantable electrode arrangement with a third electrode arrangement for inhibiting selective nerve fibers,

Fig. 7a

Representation of an electrode strip with opening,

Fig. 7b

detailed representation of an electrode strip integrated in the carrier substrate,

Fig. 7c

Alternative design of a structural element,

Fig. 8a-f

Representations of a cuff additionally reinforcing the implantable electrode arrangement,

Fig. 9

Hydraulic application structure of the implantable electrode assembly, and

Fig. 10

Flowchart for performing the electrical stimulation of a nerve fiber.

Ways to carry out the invention, industrial usability

FIG. 1 FIG. 12 is a block diagram showing the individual components of the implantable device, each interconnected via mostly bidirectional electrical communication paths, see interconnection arrow representations. The individual communication paths can be realized in the form of wire-based or wireless connection lines, via which electrical signals for informal data transmission as well as electrical energy transmission are bidirectionally transferable.

The main components of the implantable arrangement relate to the implantable electrode arrangement E, the evaluation / control unit A / S, a first comparator unit K1 electrically connected to the evaluation / control unit A / S, and a first connected likewise to the evaluation / control unit A / S Function generator F1 and a both the first function generator F1 medium or directly and with the implantable electrode assembly E electrically connected, the first signal current transformer SSW1.

In a first embodiment, the implantable electrode arrangement E corresponds to a per se known electrode arrangement as shown in FIG FIG. 2a, b is illustrated, which is cuff-like applied to a nerve fiber bundle, wherein for purposes of selective detection of electrical neuronal time signals preferably designed as Tripolanordnung first electrode structures 3 are provided, each axially on both sides of the implanted state annular first electrode strips 5 are limited, see Fig. 2a, b ,

In addition, the implantable electrode assembly E provides at least one electrode for detecting the ECG signal, for example, such an ECG signal pick-up with the aid of the reference electrodes 12 according to the in FIG FIG. 2a illustrated, implantable electrode assembly possible.

The electrical information detected with the aid of the electrode arrangement E, both the ECG signal and the neuronal electrical time signal correlated with the blood pressure, are supplied to the evaluation / control unit A / S in a time-resolved manner for further evaluation. Preferably, a timer unit T is used for the time-resolved detection and transmission of the electrical signals to the evaluation / control unit A / S. For a further better understanding of the operation of the implantable device are related to FIG. 3 the temporal relationships between an ECG signal detected by means of the second electrode arrangement applied to the carotid artery around the vagus nerve (see A), the natural pulse wave or blood pressure wave PW through the aorta (see B), for example with a dedicated blood pressure sensor is detected within the aorta in the immediate vicinity of the heart, as well as a neuronal time signal ZS derived from the neuronal, electrical signals correlated with the blood pressure (see C).

The mechanical pulse wave PW stimulates the baroreceptors in the aortic wall, as a result of which the baroreceptors emit frequency-coded neuronal electrical signals as a function of the strength of the pulse wave PW. This synchronous stimulation of many hundreds of baroreceptors produces in total the neuronal, electrical signal which can be tapped via the cuff electrode applied around the vagus nerve.

However, for a technical stimulation of the vagus nerve for the purpose of a therapeutically motivated signal overwriting of the natural neuronal electrical signals directed along the vagus nerve to the brain, it is necessary to consider at least two time delay effects, which are at technical stimulation must be considered or compensated, especially since the stimulation should be made as natural as possible, in order to avoid that the brain is permanently irritated by the technical signal intervention:
On the one hand, this relates to the time offset ZV between the beginning of the ECG signal or the R wave of the ECG signal, see Fig. 3A , and the rise of the blood pressure wave PW in the aorta, see point P1 in FIG Fig. 3B , On the other hand, this relates to the temporal offset ZV * between the stimulation and transduction of the baroreceptors and the neuronal electrical time signal ZS until it has reached the area at which the cuff electrode E is to overwrite the natural blood pressure signal. This time offset ZV * is typically selected between the point P1 and a first maximum M of the neural electric time signal ZS.

The neural, electrical time signals ZS can appear in different ways, as a rule, they have a so-called "Mexican Hat" shape and thus consist of several "oscillations". This seems surprising at first, especially since the pulse wave signal PW is not coded by the baroreceptors in "waveform". The reason for this lies in the tripolar configuration of the first electrode arrangement. Thus, the "on-chip", natural, neuronal electrical pulse wave signal runs along the length of the vagus nerve past the three electrode structures of the first electrode arrangement in the longitudinal direction and is able to polarize them successively in terms of time. In this way, the monophasic neuronal electrical signal is converted into the multiphase, neuronal electrical time signal ZS.

In addition, the derived, multi-phase, neuronal, electrical time signal ZS always lies temporally between a characteristic edge rise point P1 and a flank descent point P2 of the pulse wave PW, ie within the time window T1, which corresponds to the time duration of the pulse wave PW.

Taking into account the time offsets ZV and ZV * explained above, it applies within the time window ZF, see Fig. 3D to generate the electrical stimulation signal and to apply via the first electrode arrangement to the vagus nerve for the purpose of selective stimulation of the at least one baroreceptive nerve fiber.

The determination of the blood pressure correlated neural electric time signal ZS (see Fig. 3C) In contrast to the detection and metrological use of the ECG signal special signal processing or signal processing, especially since the signal level of the metrologically detected, correlated with the blood pressure time signals ZS is not able to stand out from the surrounding electrical noise level. In this case, the neuronal, electrical signals obtained with the aid of the implantable electrode arrangement are preferably subjected to coherent averaging, preferably with the ECG signal as trigger, all of which signal components undergo additional amplification which reproducibly follow the blood pressure. Further details can be found in the above cited contribution of Dennis TT Plachta, Oscar Cota, Thomas Stieglitz, Mortimer Gierthmuehlen, "Selective Discharge and Stimulation for a Hypertensive Implant Using Multichannel Cuff Electrodes", tm - Technisches Messen, 2013, Vol.80 (5), pp.163- 172 be removed.

With the help of the thus obtained, with the blood pressure correlated, neural, electrical time signal ZS, the FIG. 3C is shown in its time-varying amplitude profile, the time offset ZV to the ECG signal (see FIG. 3A ) to investigate. It should be noted at this point that the blood pressure-correlated, neuronal, electrical time signal ZS obtainable with the aid of the implantable arrangement corresponds only to a relative blood pressure value, ie the electrical potentials rise and fall with the blood pressure, whereas the time signal maximum does not represent an absolute blood pressure in mmHg , For absolute blood pressure determination, it is therefore necessary to provide an additional external or internal reference sensor with which the absolute blood pressure can be detected. For purposes of calibrating the device using the implantable electrode assembly obtained time signal ZS is preferably also an implantable, technical blood pressure sensor, for example, a known tipkatether, or an extracorporeal applicable blood pressure cuff. In FIG. 1 For this purpose, the reference blood pressure sensor SB is shown as a further component, which does not necessarily have to be designed as an implantable unit. Preferably, the absolute blood pressure values determined with the aid of the reference blood pressure sensor SB are likewise fed to the evaluation / control unit A / S in a time-resolved manner. For the corresponding time recording is used with the reference blood pressure sensor SB in data exchange clock UH.

In order to electrically stimulate the baroreceptive nerve fibers within the nerve bundle encompassed by the implantable electrode assembly E in a manner necessary for efficient blood pressure therapy, an analysis of the ECG signal and the neuronal electrical time signal correlated with the blood pressure is required. The relevant evaluation is carried out in the evaluation / control unit A / S with the aim of determining exactly those times at which the brain expects the baroreceptive signals transmitted via the baroreceptive nerve fibers. The technical electrical stimulation of the blood pressure signals transmitting nerve fibers should also coincide with the natural blood pressure signal supply with respect to timing, duration and also the time-varying signal waveform. As a timer or trigger signal, the ECG signal is monopolar as an artifact, for example via the reference electrodes 12 (see FIG. 2a ) and transmitted as a time signal to the evaluation / control unit A / S. In the evaluation / control unit A / S, the time offset ZV between the ECG signal and the natural pulse wave PW is determined in the following. In particular, the time difference between the R peak of the ECG signal and a characteristic signal edge point P1 along the rising initial edge of the blood pressure wave PW serves this purpose. The time offset ZV will be <200 ms in a person with a normal pulse (65 BPM) ( Fig. 3A , see timeline in seconds). Furthermore, in the context of the evaluation / control unit A / S, the characteristic pulse duration T1 of the pulse wave PW measured by the time interval of the first signal edge point P1 and a second signal edge point P2 along the falling signal edge is given.

Furthermore, within the evaluation / control unit A / S, taking into account biological delays, for example due to the transduction of a mechanical event (pulse wave) into a bioelectric signal and / or the conversion of a technical current signal into a bioelectric, neural potential and / or or a time delay caused by the characteristic line speeds along neuronal fibers, a corrected time offset ZV *, which is taken into account when generating a stimulation signal.

Thus, it is necessary to electrically stimulate the at least one baroreceptive nerve fiber within a specific time window ZF, which lies in a defined time offset ZV + ZV * to the detected ECG signal. This is done with the aid of the function generator F1, which is composed of a multiplicity of n individual pulses and correlated in phase and temporal amplitude course with the natural blood pressure, neuronal electrical signal SN (see FIG FIG. 4 A) adapted stimulation signal SSI generated. In this connection, it should be mentioned that the natural neuronal, electrical signals Sn propagating along baroreceptive nerve fibers are identical in terms of time duration T _SN , and amplitude form corresponds to the shape and pulse duration of a blood pressure pulse PW.

The function generator F1 modulates the amplitudes of the n individual pulses EP (in FIG. 4A If the stimulation signal SSI is composed of 13 individual pulses EP, in reality 100 to 200 individual pulses will result in a stimulation signal) and thus approximately maps the biological pressure profile detected in the stimulation signal SSI using the implantable electrode arrangement E as an enveloping function. To determine the time-variable amplitude curve of the stimulation signal SSI, ie the matched amplitudes of the individual pulses EP within a stimulation signal - serve the pulse duration T1 of the correlated with the blood pressure time signal ZS and its maximum amplitude A _max . Advantageously, the pulse duration T1 and the maximum amplitude A _{max are determined} within the first comparator unit K1.

Each individual pulse EP has characteristic characteristics which are FIG. 4 B are removable. Thus, each individual pulse EP has a cathodic signal part KT and an anodic signal part AT. The anodic signal part AT of each individual pulse EP has an anodic amplitude in amperes E1 and an anodic pulse width E4. Likewise, the cathodic signal portion KT has a cathodic amplitude in ampere E2 and a cathodic pulse width E3. The repetition rate E5 is measured in Hz. Not necessarily the repetition rate E5 has to correspond to a fixed frequency, but it has been found that neuronal systems, ie neuronal nerve fibers, can be stimulated best when external electrical activations follow the natural typical pattern of neuronal activity, ie a distribution function, preferably subject to a Poisson distribution. The generation of the stimulation signal SSI composed of the multiplicity n individual pulses EP preferably takes place with the first function generator F1 in such a way that the two phases of each individual pulse EP, ie the surfaces of the anodic AT and of the cathodic signal part KT are equal, since otherwise the electrode contacts, ie at least the electrode surfaces 4 of the tripolar electrode structures 3, see Fig. 2 , which would allow subsequent electrical stimulations with significantly less efficacy to be applied to the at least one selected nerve fiber within the nerve fiber bundle. Furthermore, charge imbalance can lead to corrosion due to redox reactions if the polarization builds up a DC potential and this exceeds the limits of the water window. The individual anodic and cathodic signal parts AT, KT of each individual pulse EP are generated by the first function generator F1 in the form of rectangular partial signals.

It has also proved to be advantageous that a certain "rounding" of the signal edges of each individual pulse EP in an advantageous manner with respect to a reduction of the metal contacts of the individual electrodes implantable electrode assembly effects occurring corrosion, whereby their life can be improved. Such technical signal edge rounding, in particular the Repolarisationsflanke E6, in the schematic representation in FIG. 4B bottom left illustrates, in addition to the above-mentioned, improved electrochemical properties also beneficial in terms of biological effectiveness in the electrical stimulation of at least one selected nerve fiber. For this purpose, the first function generator F1 is directly followed by a first modulator M1, see FIG. 1 , The modulator M1 is primarily capable of extending or smoothing the rectangular, repolarizing signal part AT with respect to the polarizing signal part KT, both signal parts AT, KT having uniform, ie equal signal strengths, in order to enable a complete repolarization of the electrode surfaces. Alternatively or in combination with the above measure of rounding off at least the repolarizing signal part AT, a further advantageous influence of the first modulator M1 on each of the individual individual pulses EP generated by the first function generator F1 performs a time decoupling between the cathodic signal part KT and the anodic signal part AT a time break E7 before (see FIG. 4 , lower right representation). As a result, an extremely long signal edge between the cathodic and anodal signal part KT, AT is avoided, whereby unwanted neurostimulatory artifacts can be excluded. Of course, it is also possible to modulate the time length of the break E7.

All of the above and described FIG. 4 removable individual pulse characteristics E1 to E7 can be individually matched and adjusted with the aid of the first modulator M1.

Depending on individual regulatory requirements, the implantable device may autonomously decide for purposes of leveling the blood pressure whether, when and in which strength and duration electrical stimulation signals SSI are applied to the at least one baroreceptive nerve fiber should be. For this purpose, the implantable arrangement according to FIG. 1 at least one second comparator K2 ago, which is electrically connected to the evaluation / control unit A / S. The second comparator arrangement K2, which may be structurally combined with the first comparator unit K1, compares at least one characteristic signal level of the blood pressure correlated neural time signal ZS with a reference signal, which is preferably stored in a lockup table LT, both with the evaluation - / control unit A / S and also connected to the comparator unit K2, and generates a characteristic difference level, based on the evaluation / control unit A / S at least the temporal amplitude course, ie determines the time-variable amplitude level of the stimulation signal SSI. Finally, based on at least the generated difference level value, all stimulation parameters E1 to E7 can be variably adjusted to one another so that all individual pulse forms can be selected individually in order to assemble a stimulation signal SSI to be applied to the at least one baroreceptive nerve fiber.

Of course, in addition to the reference signal stored in the lock-up table LT, further information characterizing the physiological state of the respective patient can be advantageously stored for purposes of electrical stimulation of the at least one baroreceptive fiber, such as information characterizing the state of motion of the patient Difference level value, detected absolute blood pressure etc.

Thus, in an advantageous embodiment, the implantable arrangement has an acceleration sensor BS, which is preferably integrated in the implantable module, in which the evaluation / control unit A / S the first and second comparator K1, K2, the first function generator F1 and the first signal Current transformers SSW1 are summarized. The acceleration sensor BS is electrically connected to the evaluation / control unit A / S and is thus able to forward the generated acceleration information to the evaluation / control unit A / S for further evaluation. Likewise, it is possible to have an extracorporeal on Patients attached to use acceleration sensor whose acceleration information can be fed wirelessly, for example by inductive data coupling, the evaluation / control unit A / S. The at least one, preferably triaxial, acceleration or movement sensor BS can thus detect the physical activity of the respective patient, so that movement-related increases in blood pressure can be taken into account, which are recognized as such by the implantable arrangement and not to a corresponding reduction in the blood pressure lead at least one baroceptive nerve fiber.

In addition to a possible extracorporeal training and attachment of a triaxial acceleration or motion sensor further extracorporeal units may be provided in an advantageous manner, such as an energy source ES, a memory module SM and a signal and power supply unit SES. For the transmission of all electrical signals as well as for the transmission of electrical energy is the wireless induction-based signal and energy transmission technology.

All information that is sent to the evaluation / control unit A / S, in particular the intracorporeal detected blood pressure correlated neuronal time signals ZS and all extracorporeal information supplied can be stored in the lockup table LT and updated accordingly, so that the implantable device underlying regulatory mechanism can always rely on updated information. For example, in this way, the neuronal time signals ZS correlated by the blood pressure tapped with the aid of the electrode arrangement E, which represent only relative blood pressure signals, can be calibrated with current, absolute blood pressure values that can be detected with the aid of intracorporeal or extracorporeal blood pressure measuring systems SB. Furthermore, the implantable arrangement designed in accordance with the invention enables self-regulatory monitoring of the stimulation signals applied to the at least one baroreceptive nerve fiber, by means of the electrode arrangement E, the organic feedback of the performed Stimulation is detected, so that a so-called "closed-loop control function" is feasible. Alternatively or in combination with or with the aforementioned look-up table, a further memory area may be provided for the provision of information or signals, so that signals can also be stored as such when, for example, a state estimator / Kalman filter is used for regulation and temporally past signals to influence the manipulated variable for the control.

With reference to FIG. 5 will be explained in the following two different blood pressure control modes, with which the implantable device can make a blood pressure control. In both in FIG. 5 In the diagrams shown, the respective upper graph shows the blood pressure along the time axis t. The respective lower graph in both diagrams schematically represents the stimulation amplitude of a respective stimulation signal SSI. In the case of in FIG. 5 It can be seen from the above blood pressure regulation that immediately after activation and application of a stimulation signal SSI having a stimulation amplitude A3, a depression DE that significantly reduces the blood pressure is produced. If the stimulation signal SSI is repeated with a time recurrence t1, this leads to a rapid lowering of the blood pressure until a desired blood pressure value is reached.

The blood pressure control mode B illustrated in the lower diagram, on the other hand, leads to another response of the natural, physiological blood pressure control. Thus, in this case, the stimulation signals SSI are activated and applied at a much lower stimulation amplitude A4 than in the case of the stimulation amplitude A3 in the regulation mode A explained above. Such an insufficient stimulation signal amplitude A4 does not result in an acute dent DE in the blood pressure value. If the time intervals between the individual stimulation signals SSI in the case of the control mode B also chosen appropriately large (see time axis in minutes), ie much larger than in the case of the mode A, this leads to a very slow but steady blood pressure reduction, as is the blood pressure function in the case of the control mode B can be removed. By This control mode B, also referred to as the "secondary effect", in comparison with the control mode A, referred to as the "primary effect", can save a great deal of energy for operating the implantable device. Furthermore, the burden on the nerve tissue as well as for the electrodes is considerably lower, in addition, the blood pressure can be adjusted carefully. Both the stimulation amplitude A4 and the temporal repetition rate t2 can be selected individually for setting a desired reduced blood pressure. The modus operandi designated as control mode B is preferably suitable for the treatment of chronic hypertension, whereas the control mode A, referred to as the primary effect, should be used in cases of a hypertensive crisis.

The implantable arrangement according to the invention is capable of switching autonomously, depending on the occurrence of certain blood pressure situations, between the two control modes during operation, i. If it is necessary to reduce blood pressure peaks as quickly as possible, the control mode A is suitable, but if slow blood pressure corrections are to be applied, control mechanism B is used. To decide which of the two control mechanisms are used, all the information currently recorded in the lock-up table and supplied to the evaluation / control unit A / S can be utilized.

As already in connection with FIG. 4 1, the n individual pulses EP are composed of a cathodic and anodic signal part KT and AT, so that both polarization signal areas cancel each other completely (charge-balanced stimulation), whereby a residual polarization of the respective electrodes contributing to the stimulation should be avoided , Despite these measures, it is possible that a, albeit small, residual polarization at the electrodes can not always be ruled out, as a result of which the following stimulation single pulses may be impaired both with regard to their pulse shape and pulse strength. These unwanted effects caused by residual polarizations must be ruled out.

For this purpose, a further preferred embodiment of the implantable arrangement according to the invention provides an electrode impedance measuring unit EM, see FIG. 1 which is part of the implantable module or is arranged on the carrier substrate 1 and is electrically connected to the electrode arrangement E and to the evaluation / control unit A / S. The electrode impedance measuring unit EM is designed in such a way that it makes an impedance measurement between each of the n individual pulses EP at least at the electrodes of the first electrode arrangement and thus measures its polarization. The electrode impedance measuring unit EM is further connected to a first depolarization unit EE1, which is also part of the implantable module or is attached to the carrier substrate 1. The first depolarization unit EE1 is able, in the case of a residual polarization at individual electrodes determined by the electrode impedance measuring unit EM, to depolarize it by selectively activating the corresponding electrodes selectively by means of electrical signal application. Moreover, the first depolarizing device EE1 is not only capable of detecting and correspondingly eliminating possible residual polarizations at the electrodes involved in the stimulation between each individual pulse, but rather a corresponding polarization measurement and a corresponding active depolarization even after each individual stimulation signal SSI. As a result, all individual pulses EP can be generated freely or at least largely free of polarization effects, so that each individual stimulation signal SSI is generated under the same electrical conditions with the aid of the electrode arrangement. In this way, it can be ruled out that the stimulation signals build up a subordinate DC potential in time sequence.

The implantable arrangement formed in accordance with the invention provides, in a preferred embodiment, an opposite to that in FIG FIG. 2a, b illustrated implantable electrode assembly E before a modified electrode assembly E, which in FIG. 6 which is discussed below, and which is an undesirable, but with the electrode arrangement described above possible signal propagation along the baroreceptive nerve fiber towards the heart is able to actively suppress.

For this purpose, the implantable electrode arrangement provides a third electrode arrangement 7 for inhibiting unidirectional neuronal electrical signals propagating unidirectionally along the nerve fiber bundle at the straight-cylindrical carrier substrate surface oriented in the implanted state, facing the nerve fiber bundle. The third electrode assembly 7, to which reference will now be made in detail, is activated solely in conjunction with the electrical stimulation of the at least one baroreceptive nerve fiber. For this purpose, a second function generator F2 is provided, which is also integrated in the implantable module and before and / or during the determined time window T1, see FIG. 4 , generates an electrical, so-called blocking or inhibition signal. The second function generator F2, see FIG. 1 , Further, is directly or indirectly connected to a second signal-to-current converter SSW2, which supplies the electrical inhibition signal to the third electrode arrangement 7. As with the first function generator F1, the second function generator F2 is also capable of generating individual pulses which are each composed of a polarizing and a repolarizing, rectangular partial signal. Also in this case, both partial signals neutralize each other in terms of their polarity surface, so that as far as possible no residual polarization remains on the respective electrode surfaces 9 after each individual pulse.

Furthermore, a second modulator M2 is connected between the second function generator F2 and the second signal-to-current converter SSW2, which increases and smooths a signal edge course assigned to the rectangular pulse-shaped, repolarizing partial signal AT with respect to the polarizing partial signal KT and unifies the signal strength assigned to the two component signals. The measure associated with the second modulator M2 is practiced for the same reasons as explained above for the first modulator M1. In addition to the second function generator F2, the second modulator M2 is also integrated in the implantable module. Also in the case of the second modulator M2 it is optionally additionally possible to separate the polarizing component signal from the repolarizing component signal by a zero signal level which can be generated in the second modulator M2 in each individual pulse. In this way, a long steeply falling signal edge between the two partial signals is avoided, which could possibly lead to irritating inhibition effects or additional stimulation of the nerve fibers under the external electrodes (so-called anodic break excitation).

With the aid of the third electrode arrangement 7, the inhibition can be realized either by means of a so-called anodal block or by application of sinusoidal signals of frequencies in the kilohertz range, the so-called HF block. In the case of the anodal block, at least one of the third electrode surfaces is anodically polarized, thereby producing a voltage potential prevailing at the location of the efferent nerve fiber, by which an activating stimulation of the corresponding nerve fiber is suppressed. In this case, an additional modulation by means of the second modulator M2 is not required. Likewise, an inhibition can be achieved by means of a high-frequency signal application in which a high-frequency electrical inhibition signal is applied to at least one selected third electrode surface, whereby the electrical signal transmission mechanisms along the efferent nerve fibers come to a standstill for a short time.

The third electrode assembly 7 for targeted inhibition of unidirectional, preferably in the direction of the heart, along the at least one selective baroreceptive nerve fiber propagating stimulation signals is also connected to the electrode impedance measuring unit EM to detect possible residual polarizations at the third electrode assembly 7 associated electrode surfaces 9, 8 , For a corresponding Entpolarisierung possible residual polarizations also provides a second Entpolarisierungseinrichtung EE2, both the residual polarizations between individual pulses as well as between possible successive inhibition signals can be eliminated by means of metered electrical activation of individual electrodes.

For the purpose of electrical protection of the implantable device in terms of EMP protection and magnetic coupling by MRI, a corresponding unit EMP is integrated within the implantable module. This unit monitors the inputs of the electrode and allows decoupling in case of externally evoked potential fluctuations. In addition, the EMP unit has a magnetic field sensor which activates a temporary self-protection program when detecting a strong DC field.

FIG. 6 shows a schematic plan view of a preferably formed, implantable sleeve electrode E, on which preferably consists of polyimide carrier substrate 1, in addition to the location-selective detection of neuronal electrical signals and selective electrical stimulation of individual nerve fibers provided first electrode assembly 2 serving for inhibiting at least one selected nerve fiber third electrode arrangement 7 is applied. To avoid repetition, reference is made to the explanation of the individual electrodes of the first electrode arrangement 2 and the second electrode arrangement 12 to the above description of FIG FIGS. 2a and b.

The third electrode arrangement 7, which extends along the efferent, here to the heart H, leading to signal propagation, comprises two axially spaced third electrode strips 8, between which a third electrode structure 13 is centrally provided which consists of four third electrode surfaces 9 arranged separately from one another. All of the electrodes 8, 13 of the third electrode arrangement 2 are connected or connectable to the evaluation / control unit A / S via electrical conductor tracks L applied to or in the carrier substrate 1. The electrical interconnects L can optionally have a separable connection structure V.

Optionally, the third electrode arrangement 2 comprises optical waveguide arrangements 10 which each comprise four separate optical waveguide openings 11 distributed in the circumferential direction U. The optical waveguides LI to the individual optical waveguide openings or apertures 11 extend within the carrier substrate 1 and can be combined on the proximal side with a uniform light source LQ or with separate light sources LQ different wavelengths optogenetically selectively activated stimuli and / or optically activated and selective inhibition along certain To cause nerve fibers.

The geometric shape and size choice of the individual electrodes, ie, the first and third electrode strips 5, 8 and the first and third electrode surfaces 4, 9 can basically be made individually matched and are in particular based on the diameter of the nerve fiber bundle around which the implantable cuff electrode E can be applied. Thus, the extension of the first and third electrode structures and electrode strips, and possibly the optical waveguide arrangements 10 oriented in the circumferential direction U, preferably corresponds to the length of the peripheral edge of the nerve fiber bundle to be wrapped with the sleeve electrode E. The axial distance of the tripolar electrode arrangement should preferably be adapted to the diameter and the resulting distance of the so-called Ranvier Schnürringe in myelinated nerve fibers of the nerve fibers to be excited. In the in FIG. 6 illustrated embodiment, the electrodes are shown as rectangular electrode surfaces. In an advantageous manner, in particular for the purpose of avoiding field line densifications occurring at electrode rectangular edges, it is advisable to form the electrode surfaces at least with rounded corners.

In humans, it is important to inhibit or activate certain large and myelinated fibers. This is possible only at the points along the nerve fiber which these fibers are not myelinated, ie on the so-called Ranvier rings. With increasing diameter of the nerve fiber, the intervals, ie the axial distances between the Ranvierschen rings larger, accordingly, it is the axial distance between the two axially spaced first electrode strips 5 in about the same length as the axial distance of the rings or slightly larger to choose to sufficiently large statistical probability to reach the Ranvier rings of very large fibers. The same applies preferably also to the axial spacing of the third electrode strips 8.

The total axial extension of the entire cuff electrode E should be adapted to the intracorporeal size ratios of the respective nerve fiber bundle and typically should not exceed 4 cm.

The reference electrode surfaces 12, which are attached to the back of the carrier substrate 1, are used for detecting the ECG signal and, if necessary, the intracorporeal detectable noise level.

In addition, the carrier substrate 1 has at least one, preferably two or three openings 14 reinforced by metal ring structures, which serve for fastening the implanted electrode arrangement CF to the nerve fiber bundle. The attachment takes place with the aid of a surgical thread which is threaded at least once through the openings 14 and in which the tissue surrounding the nerve fiber bundle is sutured. In contrast to the area 1B of the carrier substrate rolled up to form a straight cylinder, on which the first and second electrode arrangements 2 and 7 are applied, so that they touch the epineurium of the nerve fiber bundle surface in the implanted state, the carrier substrate 1 adjoining the carrier substrate area 1B is in Style of a flat flag laterally from the nerve fiber bundle and protrudes into the surrounding tissue. The metal ring structures 14 are intended to help mechanically secure the fastening forces acting along the surgical thread and to prevent drastic damage to the support substrate.

For cuff-like wrapping of the implantable electrode arrangement E about a nerve fiber bundle (not further shown), the third electrode arrangement 7 is to be arranged on the side H leading to the heart along the nerve fiber bundle. The first, the selective detection and selective stimulation of localized nerve fibers serving electrode assembly 2 is attached along the nerve fiber bundle brain side G.

Preferably, the first and third electrode strips 5, 8 and the first and third electrode surfaces 4, 9 are vapor-deposited or sputtered onto the carrier substrate, galvanic amplification is conceivable. Laser structuring of thin metal foils is also possible as a technology. For permanent joining, in particular of the first and third electrode strips 5, 8 to the carrier substrate 1, the electrode strips have local openings 15, see Figure 7a through which at least partially the polymer material of the carrier substrate 1 passes or protrudes. The electrode surface 16 of each of the first and third electrode strips 5, 8 are otherwise arranged flush with the carrier substrate upper side 1 'and contact the surface of the nerve fiber bundle directly.

In order to permanently improve the joining of the electrode strips 5, 8, it is proposed in a preferred exemplary embodiment to integrate the electrode strips largely into the carrier substrate in the following manner, see FIG. 7b :
The electrode strips 5, 8 each have a metallic base plate 17, which provides an upper side 18 and a lower side 19. Integral with the upper side 18 of the base plate 17 are distributed over the upper side 18, preferably over the entire upper surface, orthogonal raised structural elements 20 are provided, preferably in the form of columnar, ribbed, web or sleeve-like extensions, over one of the carrier substrate surface 1 '. facing surface region 21, which can come in direct contact with the epineurium of the nerve fiber bundle. In addition, an adhesive layer 22 is advantageously at least between the bottom 19 and the base plate 17 surrounding Polymer material of the carrier substrate 1 is provided. The adhesion promoter layer 22 can also be applied on the upper side 18. Particularly suitable primer layers consist of silicon carbide (SiC) and diamond like carbon (DLC). Preferably, the electrode strips 5, 8 are made of iridium oxide, which is one of the materials with one of the highest charge transfer capacities.

A further improved variant for the formation of the structural elements 20, which are applied distributed on the upper side of the base plate 17, is shown in FIG FIG. 7c illustrated. FIG. 7c shows the longitudinal section through a structural element 20 having an orthogonal to the top 18 of the metallic base plate 17 oriented longitudinal extent LA, along which the structural element 20 at least a second surface portion 23 provides, which is oriented parallel to the top 18 of the metallic base plate 17 and on which Adhesive layer 22 or a bonding agent layer assembly 22 'is applied. The second surface region 23 is spaced from the first surface region 18 and completely surrounded by the biocompatible polymer separated by the adhesion promoter layer (22) and the adhesion promoter layer arrangement (22 '). The second surface area is as from the FIG. 7c can be seen, the upper side 18 of the base plate 17 facing oriented. Of course, it is additionally possible and advantageous to provide the adhesion promoter layer 22 or the adhesion promoter layer arrangement 22 'both on a third surface region 24 which lies opposite the second surface region 23 and / or on the upper and / or lower side 18, 19 of the base plate 17.

The number and arrangement of the individual structural elements 20 can be chosen arbitrarily, but are preferably geometrically ordered constellations KO, such as. Square, pentagonal, hexagonal or higher order arrangement pattern, as is known from FIG. 7b can be seen.

In the FIGS. 8a to f a cuff M which partially encloses the carrier substrate 1 of the implantable cuff electrode CE is shown Area of the carrier substrate 1 both at its lower and upper side, which adjoins directly to the carrier substrate area 1B and in contrast to the carrier substrate area 1B is not self-linearly deformed in the way of a material-inherent mechanical bias and in this way flush with the epineurium of the nerve fiber bundle in implanted state is brought into abutment.

The sleeve M serves primarily for improved handling of the implantable sleeve electrode CE, which requires particularly careful handling by the surgeon on account of its very low carrier substrate thickness and the filigree electrode arrangements applied to the carrier substrate surface. The sleeve M is preferably formed in one piece and has a sleeve lower part Mu and a sleeve upper part Mo, both of which are hingedly connected via a living hinge hinge 25, see FIGS. 8b and 8c , The sleeve bottom part Mu has a recess 26 embedding the carrier substrate 1 into which the carrier substrate 1 can be inserted. In the inserted state, the lower sleeve part Mu comprises the carrier substrate 1 in the FIG. 8b removable, framing manner, that is, the lower sleeve part MU protrudes laterally below the carrier substrate 1.

The sleeve upper part Mo connected in one piece with the sleeve bottom part Mu via the hinge joint 25 is adapted in shape and size to the sleeve bottom part Mu and likewise has the recess bottom 27 embedding the carrier substrate 1, like the sleeve bottom part Mu, so that in the closed state of the sleeve M the carrier substrate 1 in the in FIG. 8a hermetically, wherein only the carrier substrate region 1B protrudes from the sleeve M.

In addition to improved handling, the cuff M also serves in particular for improved fixation of the cuff electrode CE relative to the nerve fiber bundle. For this purpose, the sleeve upper and lower sides Mo, Mu each provide attachment openings 14 ', see Fig. 8a, b . d that coincide with the introduced within the carrier substrate 1 mounting holes 14 in the collapsed state of the sleeve M are. In this way it is possible to guide a surgical suture 28 through the apertures 14, 14 'of the cuff electrode CE encompassed by the cuff M. In this way, the metal ring encased mounting opening 14 of the sleeve electrode CE can be relieved by the introduced within the sleeve M mounting opening 14 '. Preferably, the sleeve M is made of a stable plastic material, for example of parylene. To further increase the strength, the Mo and Mu can also consist of a polymer hybrid (eg, parylene (inside) and silicone rubber outside). This hybrid has the advantage that the stability of the parylene is combined with the tear strength of the silicone. In a preferred embodiment, the attachment openings 14 'inside the sleeve M are made reinforced by appropriate material thickening.

In the upper part of the sleeve Mo opening windows 29 are introduced, which ensure free access to the reference electrode surfaces 12. In FIG. 8e a cross-section through this is represented by the carrier substrate 1 encompassed by the sleeve M, on the upper side of which reference electrode surfaces 12 are introduced, which remain freely accessible through the opening windows 29 introduced inside the sleeve upper part Mo. Preferably, the opening windows 29 comprise the reference electrode surfaces 12 with a sloping boundary edge 29 ', so that it is ensured that the reference electrode surfaces 29 can come into body contact with the surrounding tissue over the entire surface.

To ensure that the cuff M remains in a closed state, interlocking structures V are arranged between the cuff top and bottom parts Mo, Mu, which consist, for example, of a pin 30 and a recess 31 arranged opposite one another, see FIGS. 8c and f. When folding the cuff upper and lower part, the pins 30 are subjected to force in the corresponding recess 31, in which the pin 31 is held by friction, permanently. In Fig. 48, the closed state a locking structure V illustrated. In this case, the pin 30 mounted on the sleeve top Mo protrudes through a corresponding opening introduced in the carrier substrate 1 and terminates at the end within the recess 31 of the sleeve base Mu. Of course, alternative embodiments for the locking structures are conceivable, for example in the form of suitably designed locking mechanisms.

In FIG. 9 another embodiment is illustrated, which facilitates facilitated implantation of the solution formed according to the sleeve electrode CE. Within the carrier substrate 1, a fluid channel system 32 is incorporated, which is completely covered by the carrier substrate 1. The fluid channel system 32 extends substantially in the region of the carrier substrate region 1B, which assumes the shape of a graduated cylinder due to a material-inherent bias without external force by means of an autonomous self-winding. If, on the other hand, the fluid channel system 32 is filled with a fluid, preferably water, then the water pressure forming along the fluid channel system 32 can just clamp the carrier substrate region 1b against the material-inherent winding forces. For this purpose, the fluid channel system 32 has in the circumferential direction of the lateral surface of the self-forming graduated cylinder extending fluid channel branches 33, which force the required extension of the carrier substrate area 1B in the filled state.

For filling the fluid channel system 32 at least two channel openings 34 are provided within the carrier substrate 1, whose size and arrangement are dimensioned such that they fluid-tight at inlet and outlet openings of extending within the sleeve M Fluidzu- or discharges 35, 36 open. The inlet and outlet lines 35, 36 running inside the cuff M are fluidically connected to a fluid control system 37, which can be actuated by an operator.

In the case of implantation, the fluid channel system 32 is filled with a fluid, whereby the carrier substrate region 1B is stretched. In this state, the Operate the cuff electrode CE exactly at a predetermined location along the nerve bundle. Subsequently, the emptying of the fluid channel system 32 is performed by the surgeon, whereby the carrier substrate area 1B automatically wraps around the nerve fiber bundle. As a final step, the cuff electrode CE is fixed to the surrounding tissue with a suture thread through the attachment holes 14 'provided in the cuff.

In an advantageous embodiment of the above fluid channel system 32, it is conceivable to fill this with a shape memory metal shape memory polymer. For purposes of activation, the channel openings 34 are provided with metallized contacts, via which an electrical voltage along the leads 35, 36 for deployment of the implantable electrode assembly CE via a correspondingly modified controller 37 can be applied until the electrode is finally placed.

• I) Start: Aktivierung der implantierbaren Anordnung E entweder manuell oder automatisch, hierzu wird die Auswerte-/Steuereinheit in Form eines Microcontrollers initiiert (A/S, Fig.1)
• II) Erfassung des EKG Signals mittels der Elektroden 12 der Manschettenelektrode E, siehe Fig. 6. Die Auswerte-/Steuereinheit A/S validiert hierbei die R-Zacke und separiert etwaige EMP Fehler aus dem Signal, wobei mehrere Durchläufe monitoriert werden. Die Auswerte-/Steuereinheit A/S bestimmt hierbei die Zuverlässigkeit, mit der die R-Zacken erkannt werden. Schließlich ermittelt die Auswerte-/Steuereinheit A/S die Herzschlagrate.
• III) Erfassung des Blutdrucksignals SN mittels der ersten Elektrodenflächen 4, der ersten Elektrodenstreifen 5 sowie der EKG- Elektrodenflächen 12, der Manschettenelektrode E. Dies erfolgt durch kohärentes Mitteln der Signale der mittleren Reihe der ersten Elektrodenflächen 4, getriggert durch die Anstiegsflanke des zuvor ermittelten EKG Signales.
• IV) Entscheiden ob Blutdruckänderung vorliegt.
• IVa) Hierbei erfragt die Auswerte-/Steuereinheit A/S einen aktuellen ReferenzBlutdruck (SB) und vergleicht bzw. kalibriert die Amplitude des Referenzsignales mit dem Blutdrucksignals SN
• IVb) Validierung des Blutdruckes und der Stimulationsposition, falls Blutdruckänderung vorliegt, siehe y. Die Auswerte-/Steuereinheit A/S fragt die Look up Tabelle LT nach bereits für diesen Patienten abgelegten Blutdrucksignalwerten SN sowie Zeit-Intervallen ZV und ZV* ab und vergleicht diese mit dem im Wege der Mittelung erfassten Blutdrucksignal SN. Die Auswerte-/Steuereinheit A/S ermittelt das "beste" SN einer Elektrode, diese wird als kommende Stimulationselektrode im Arbeitsspeicher markiert
• V) Bestimmung des zeitlichen Versatzes ZV zwischen EKG-Signal und Blutdruckreferenzsignal. Hierbei ermittelt die Komparatoreinheit K1 den zeitlichen Versatz ZV zwischen R-Zacke und Anstiegsschwellwert und Referenzblutdruck.
  Die Komparatoreinheit K2 ermittelt den zeitlichen Versatz ZV* zwischen dem Anstiegsschwellwert des Referenzsignales und dem über die Elektrode erfassten neuronalen Blutdrucksignal siehe ZS in Fig. 3 und SN in Fig. 4. Aus dem Referenzblutdruck werden Beginn P1 und Ende P2 der Pulswelle PW bestimmt. Dieses Intervall ergibt T1, siehe auch Figur 3B und C. Das Intervall T1 wird um den zeitlichen Versatz ZV + ZV* versetzt und ergibt das Intervall ZF. (Siehe Fig. 3)
• VI) Entscheidung zur Stimulation und Auswahl der Stimulationsparameter:
  Die Auswerte-/Steuereinheit A/S ermittelt die Uhrzeit UH und die aktuelle Lage und Bewegung des Patienten mit dem Beschleunigungssensor (BS).
  Die Auswerte-/Steuereinheit A/S ermittelt ferner die Impedanzen der Stimulationselektrode über den Inter-Stimulus Impedanz Detektor. Basierend auf den erhobenen Blutdruckwerten, der Herzschlagrate, der Aktivität des Patienten und dem Ausbleiben eines anderslautenden Steuerkommandos, z.B. ausgelöst durch externes Signal durch Radio Com Modul (SES), ein Fehlfunktionssignal einer Komponente des Implantates (z.B. eines IC der Stimulationsseite), oder der Detektion eines starken statischen Magnetfeldes (EMP), etc, entscheidet die Auswerte-/Steuereinheit A/S, ob eine Stimulation erfolgen soll, ja (y) oder nein (n).
• VIa) Stimulationsreferenzwerte. Die Auswerte-/Steuereinheit A/S vergleicht die erhobenen Parameter mit bereits gespeicherten in der Look up Tabelle LT und dem Speichermodul SM und wählt passende Stimulationsparameter aus (passend bedeutet wie "stark" und wie "lange" muss stimuliert werden um den Blutdruck um x% zu senken).
  Die Stimulationskoordinaten wie (ZF, Anzahl und Form der Pulse werden dem "aktivierenden" Funktionsgenerator F1 (binär) mitgeteilt. Falls parallel selektiv Inhibiert werden muss, werden die passenden Stimulationsparameter für die selektive Inhibition an den Funktionsgenerator F2 (binär) weitergegeben.
• Vlla) Die Auswerte-/Steuereinheit A/S entscheidet über das Inhibitionsverfahren (HF oder anodaler Block)
• Vllb) Die Auswerte-/Steuereinheit A/S entscheidet über den Stimulationsmodus A oder B (siehe Fig. 5)
• Vlllb) Vorbereitung/Modulation der aktivierenden Stimulationsparameter gemäß Modus A:
  Wird ein A-Modus für eine schnelle Intervention gewählt, wird ein fester Stimulationssweep mit definierter Anzahl an Einzelpulsen vorbereitet (Dauer ist nicht korreliert mit dem ZF Interval, sondern wird einer Tabelle entnommen), der mit vordefinierten Pausen wiederholt wird (Siehe Fig. 5 Modus A).
  Die Auswerte-/Steuereinheit A/S übergibt ein Template an den ersten Funktionsgenerator F1, der das Spannungssignal generiert, das an den Modulator M1 übertragen wird.
• VIIIc) Vorbereitung/Modulation der aktivierenden Stimulationsparameter gemäß Modus B:
  Wird ein B-Modus gewählt, müssen die Einzelpulse weiter optimiert werden. Der erste Funktionsgenerator F1 erstellt ein analoges Template eines Stimulationsintervals (SSI) und passt eine definierte Anzahl an einzelnen biphasischen Pulsen in das Interval ZF ein. Hierbei wird das Stimulationssignal dem biologischen Signal angepasst. Der Referenzblutdruckverlauf wird als umhüllende Funktion über die Amplitude des Einzelpulse gelegt (siehe Fig. 4A). Der erste Funktionsgenerator F1 übergibt die Tabelle mit dem vorbereiteten Stimulationssweep an den Modulator M1.
• IX) Anpassung der Phasen der Einzelpulse des Sweeps:
  Der Modulator M1 ist für beide Modi zuständig und variiert die beiden Phasen jedes einzelnen Pulses (siehe Fig. 4 B) um eine für den individuellen Patienten ideale Einzelpulsform zu erstellen. Der Modulator M1 übergibt das "fertige" Spannungssignal in Form eines Sweeps an den Signal-Strom-Umwandler (SSW1).
• Xb) Durchführung der aktivierenden Stimulation:
  Der Signal-Strom-Umwandler SSW1 wartet auf das EKG Trigger Signal und wartet bis das "aktive Fenster für die Stimulation ZF" erreicht ist und überträgt den Stimulationssweep auf die zuvor ausgewählte Stimulationselektrode. Zwischen jedem Einzelpuls wird die Impedanz des Stimulationskontaktes durch die Elektrodenimpedanzmesseinheit EM erfasst. Wird eine Polarisation vermittels der Auswerte-/Steuereinheit A/S detektiert gibt diese dem aktiven Polarisationskompensator EE1 den Befehl zwischen jedem Puls eine kleine Extraladung zur Kompensation durch den Stimulationskontakt zu leiten. Reicht diese Interstimulationskompensation nicht aus, wird zudem der nach Beendigung des Sweeps der Intersweep-Kompensator aktiviert und gleicht eine Polarisation aus.
• VIIIa) Vorbereitung/Modulation der inhibierenden Stimulationsparameter:
  Die Auswerte-/Steuereinheit übergibt dem Funktionsgenerator F2 ein Stimulationsintervall für die Inhibition. In aller Regel ist dies länger als die aktivierende Stimulation, d.h. es beginnt kurz davor und endet nach der aktivierenden Stimulation.
  Die Auswerte-/Steuereinheit A/S legt fest, ob der zweite Funktionsgenerator F2 einen anodalen Block legt, d.h. nur monophasischen Block oder ob ein HF-Block erfolgen soll. Der Funktionsgenerator 2 erstellt zudem entsprechend ein Stimulations(Spannungs-)Template. Im Falle eines HF-Blockes übergibt der F2 das Spannungssignal dem Modulator M2, um die einzelnen Phasen zu "glätten".
• Xa) Durchführung der inhibierenden Stimulation:
  Der Signal-Strom-Umwandler SSW2 setzt das Signal entweder als anodaler Block des F2 oder als HF-Block des M2 in ein Stromsignal um und leitet es über die Inhibitionselektrode 9 der Reihe 13, siehe Figur 6. Die Elektrodenimpedanzmesseinheit EM überwacht die Polarisierung der inhibierenden Elektroden 9 und aktiviert über die Auswerte-/Steuereinheit A/S im Bedarfsfall die Entpolarisierungseinheit EE2 zur Kompensation.
  Beim HF-Block kann beides erfolgen interstimulus und intersweep, beim anodalen Block wird nur der Intersweepkomensator aktiv.
• XI) Auswertung der Stimulation:
  Die Auswerte-/Steuereinheit A/S ermittelt die Veränderung der Blutdruckkurve und leitet eine Wiederholung ein. Im Falle des B-Modus kann als primärer Stimulationsparameter variiert werden wieviele Herzschläge die Stimulation pausiert. Über diese Funktion erfolgt die (patientenpezifische) Rückkopplung der Wirkungsweise des Implantates.
  Der Erfolg der Stimulation wird in einen Speicher geschrieben um für spätere Vergleiche benutzt werden zu können.

Bezugszeichenliste 1 Trägersubstrat 1' Trägersubstratoberfläche 1B Trägersubstratbereich 2 erste Elektrodenanordnung 3 erste Elektrodenstrukturen 4 erste Elektrodenflächen 4a axiale Erstreckung der ersten Elektrodenflächen 4U in Umfangsrichtung orientierte Erstreckung der ersten Elektrodenflächen 5 erste Elektrodenstreifen 6, 6' Signaldetektor und -generator 7 dritte Elektrodenanordnung 8 dritte Elektrodenstreifen 9 dritte Elektrodenflächen 9a axiale Erstreckung der dritten Elektrodenflächen 9U in Umfangsrichtung orientierte Erstreckung der dritten Elektrodenflächen 10 Lichtwellenleiteranordnung 11 Lichtwellenleiteröffnungen 12 Zweite Elektrodenanordnung, EKG-Elektrodenflächen 13 dritte Elektrodenstruktur 14 Befestigungsöffnungen 15 Öffnung 16 Elektrodenstreifenoberfläche 17 Basisplatte 18 Oberseite 19 Unterseite 20 Strukturelement 21 Oberflächen bereich 22 Haftvermittlerschicht 22' Haftvermittlerschichtanordnung 23 Zweiter Oberflächenbereich 24 dritter Oberflächenbereich A Axiale Richtung A/S Auswerte-/Steuereinheit A3, A4 Amplitude Amax Maximale Amplitude AT Anodischer Signalteil BS Beschleunigungssensor DE Delle E Implantierbare Elektrodenanordnung, Manschettenelektrode E1 Anodische Amplitude E2 Kathodische Amplitude E3 Kathodische Pulsbreite E4 Anodische Amplitude E5 Wiederholrate E6 Repolarisationsflanke E7 Pause, Nullpegel zwischen anodischer und kathodischer Amplitude EE1, EE2 Entpolarisierungseinheit EKG EKG-Zeitsignal EM Elektrodenimpedanzmesseinheit EMP Schutzeinheit gegenüber Elektromagnetischer Pulseinwirkung EMP/MRT EP Einzelpuls ES Energiespeicher / Energiequelle F1, F2 Funktionsgenerator G Gehirn H Herz KO Geometrische Konstellation KT Kathodischer Signalteil L Leiterbahn LA Längsachse des Strukturelementes LI Lichtwellenleiter LQ Lichtquelle(n) LT Look/up - Tabelle M Maximum M1, M2 Modulator NF Nervenfaser NFB Nervenfaserbündel P1, P2 Charakteristische Phasenpunkte längs des Zeitsignals PW Pulswelle, Blutdruckwelle R R-Zacke des EKG-Signals SB Blutdrucksensor SES Signal- und Energieversorgungseinheit SM Speicher Modul SN Natürliches neuronales elektrisches Signal SSI Stimulationssignal SSW1, SSW2 Signal-Strom Wandler T Timereinheit T1 Zeitdauer der Pulswelle T_SN Pulsdauer eines natürlichen neuronalen, elektrischen Signals U Umfangsrichtung UH Uhr V Verbindungsstruktur ZF Zeitfenster ZS Zeitsignal ZV, ZV* Zeitversatz In FIG. 10 Fig. 3 illustrates a flow chart from which the sequence of single-step actions for blood pressure control through selective electrical stimulation of nerve fibers may be taken. It is believed that for purposes of stimulation, in FIG. 6 illustrated electrode assembly is applied locally to the vagus nerve with which the inhibition function is possible. Should it be possible to dispense with an inhibition, the electrode arrangement is also suitable as it were FIG. 2a , The further explanation also refers to the in FIG. 1 Components of the implantable arrangement according to the invention E. In order to avoid repetition, it should be stated that the decision points denoted by y correspond to a "yes" and the decision points designated by n correspond to a "no".

• I) Start: Activation of the implantable device E either manually or automatically, for this purpose, the evaluation / control unit is initiated in the form of a microcontroller (A / S, Fig.1 )
• II) detection of the ECG signal by means of the electrodes 12 of the sleeve electrode E, see Fig. 6 , The evaluation / control unit A / S validates the R-wave and separates any EMP errors from the Signal, where several passes are monitored. The evaluation / control unit A / S determines the reliability with which the R-waves are detected. Finally, the evaluation / control unit A / S determines the heart rate.
• III) Detection of the blood pressure signal SN by means of the first electrode surfaces 4, the first electrode strips 5 and the ECG electrode surfaces 12, the cuff electrode E. This is done by coherently averaging the signals of the middle row of the first electrode surfaces 4, triggered by the rising edge of the previously determined ECG signal.
• IV) Deciding whether blood pressure change is present.
• IVa) In this case, the evaluation / control unit A / S requests a current reference blood pressure (SB) and compares or calibrates the amplitude of the reference signal with the blood pressure signal SN
• IVb) Validation of blood pressure and pacing position in case of blood pressure change, see y. The evaluation / control unit A / S queries the look-up table LT for blood pressure signal values SN already stored for this patient as well as time intervals ZV and ZV * and compares these with the averaged blood pressure signal SN. The evaluation / control unit A / S determines the "best" SN of an electrode, which is marked as the upcoming stimulation electrode in the main memory
• V) Determination of the time offset ZV between ECG signal and blood pressure reference signal. In this case, the comparator unit K1 determines the time offset ZV between the R wave and the rise threshold value and the reference blood pressure.
  The comparator unit K2 determines the time offset ZV * between the rise threshold value of the reference signal and the neural blood pressure signal detected via the electrode, see ZS in FIG Fig. 3 and SN in Fig. 4 , Out At the reference blood pressure, the beginning P1 and the end P2 of the pulse wave PW are determined. This interval gives T1, see also FIGS. 3B and C , The interval T1 is offset by the time offset ZV + ZV * and results in the interval ZF. (Please refer Fig. 3 )
• VI) Decision to Stimulate and Select Stimulation Parameters:
  The evaluation / control unit A / S determines the time UH and the current position and movement of the patient with the acceleration sensor (BS).
  The evaluation / control unit A / S also determines the impedances of the stimulation electrode via the inter-stimulus impedance detector. Based on the collected blood pressure values, the heart rate, the activity of the patient and the absence of a different control command, eg triggered by external signal by Radio Com Module (SES), a malfunction signal of a component of the implant (eg an IC of the stimulation side), or the detection a strong static magnetic field (EMP), etc., the evaluation / control unit A / S decides whether a stimulation is to take place, yes (y) or no (n).
• VIa) stimulation reference values. The evaluation / control unit A / S compares the ascertained parameters with those already stored in the look-up table LT and the memory module SM and selects appropriate stimulation parameters (suitably means "strong" and "long" must be stimulated to increase the blood pressure by x % to lower).
  The stimulation coordinates such as (IF, number and shape of the pulses are communicated to the "activating" function generator F1 (binary) If parallel inhibition is required in parallel, the appropriate stimulation parameters for the selective inhibition are passed to the function generator F2 (binary).
• Vlla) The evaluation / control unit A / S decides the inhibition procedure (HF or anodal block)
• Vllb) The evaluation / control unit A / S decides on the stimulation mode A or B (see Fig. 5 )
• VIIIb) Preparation / modulation of the activating stimulation parameters according to mode A:
  If an A-mode is selected for rapid intervention, a fixed stimulation sweep with a defined number of individual pulses is prepared (duration is not correlated with the IF interval, but is taken from a table), which is repeated with predefined pauses (See Fig. 5 Mode A).
  The evaluation / control unit A / S transfers a template to the first function generator F1, which generates the voltage signal which is transmitted to the modulator M1.
• VIIIc) Preparation / Modulation of the Activating Stimulation Parameters According to Mode B:
  If a B mode is selected, the individual pulses must be further optimized. The first function generator F1 creates an analog template of a stimulation interval (SSI) and fits a defined number of individual biphasic pulses into the interval ZF. In this case, the stimulation signal is adapted to the biological signal. The reference blood pressure curve is placed as an enveloping function over the amplitude of the individual pulses (see Fig. 4A ). The first function generator F1 transfers the table with the prepared stimulation sweep to the modulator M1.
• IX) Adjustment of the phases of the individual pulses of the sweep:
  The modulator M1 is responsible for both modes and varies the two phases of each individual pulse (see Fig. 4B) to create an ideal single pulse shape for the individual patient. The modulator M1 passes the "ready" voltage signal in the form of a sweep to the signal-to-current converter (SSW1).
• Xb) Carrying out the activating stimulation:
  The signal-to-current converter SSW1 waits for the ECG trigger signal and waits until the "active stimulation window ZF" is reached and transmits the stimulation sweep to the previously selected stimulation electrode. Between each individual pulse, the impedance of the stimulation contact is detected by the electrode impedance measuring unit EM. If a polarization is detected by means of the evaluation / control unit A / S, this gives the active polarization compensator EE1 the command between each pulse to conduct a small extra charge for compensation by the stimulation contact. If this inter-stimulation compensation is insufficient, the intersweep compensator is also activated after the sweep has been completed and compensates for a polarization.
• VIIIa) Preparation / Modulation of the Inhibitory Stimulation Parameters:
  The evaluation / control unit gives the function generator F2 a pacing interval for the inhibition. As a rule, this is longer than the activating stimulation, ie it begins shortly before and ends after the activating stimulation.
  The evaluation / control unit A / S determines whether the second function generator F2 sets an anodal block, ie only monophasic block or whether an RF block is to take place. The function generator 2 also creates a stimulation (voltage) template accordingly. In the case of an RF block, the F2 passes the voltage signal to the modulator M2 to "smooth" the individual phases.
• Xa) Carrying out the inhibitory stimulation:
  Signal-to-current converter SSW2 converts the signal either as an anode block of F2 or as an RF block of M2 into a current signal and conducts it across series 13 inhibiting electrode 9, see FIG. 6 , The electrode impedance measuring unit EM monitors the polarization of the inhibiting electrodes 9 and activates the depolarization unit EE2 for compensation via the evaluation / control unit A / S if necessary.
  In the HF block, both can be done interstimulus and intersweep, in the anodal block only the intersweep compensator becomes active.
• XI) Evaluation of the stimulation:
  The evaluation / control unit A / S determines the change in the blood pressure curve and initiates a repetition. In the case of B-mode, it is possible to vary as the primary stimulation parameter how many heartbeats pause the stimulation. Via this function, the (patient-specific) feedback of the mode of action of the implant takes place.
  The success of the stimulation is written into a memory to be used for later comparisons.

LIST OF REFERENCE NUMBERS 1 carrier substrate 1' Carrier substrate surface 1B Carrier substrate region 2 first electrode arrangement 3 first electrode structures 4 first electrode surfaces 4a axial extension of the first electrode surfaces 4U in the circumferential direction oriented extension of the first electrode surfaces 5 first electrode strips 6, 6 ' Signal detector and generator 7 third electrode arrangement 8th third electrode strips 9 third electrode surfaces 9a axial extension of the third electrode surfaces 9U in the circumferential direction oriented extension of the third electrode surfaces 10 Optical fiber array 11 Fiber optic ports 12 Second electrode arrangement, ECG electrode surfaces 13 third electrode structure 14 mounting holes 15 opening 16 Electrode strip surface 17 baseplate 18 top 19 bottom 20 structural element 21 Surface area 22 Bonding layer 22 ' Bonding layer arrangement 23 Second surface area 24 third surface area A Axial direction A / S Evaluation / control unit A3, A4 amplitude Amax Maximum amplitude AT Anodic signal part BS accelerometer DE dent e Implantable electrode assembly, cuff electrode E1 Anodic amplitude E2 Cathodic amplitude E3 Cathodic pulse width E4 Anodic amplitude E5 repetition E6 Repolarisationsflanke E7 Pause, zero level between anodic and cathodic amplitude EE1, EE2 Entpolarisierungseinheit ECG ECG time signal EM Electrode impedance measurement unit EMP Protection unit against electromagnetic pulse effect EMP / MRT EP Single pulse IT Energy storage / energy source F1, F2 function generator G brain H heart KO Geometric constellation KT Cathodic signal part L conductor path LA Longitudinal axis of the structural element LI optical fiber LQ Light source (s) LT Look / up table M maximum M1, M2 modulator NF nerve fiber NFB Nerve fiber bundles P1, P2 Characteristic phase points along the time signal PW Pulse wave, blood pressure wave R R-wave of the ECG signal SB Blood Pressure Sensor SES Signal and power supply unit SM Memory module SN Natural neuronal electrical signal SSI stimulation signal SSW1, SSW2 Signal-current converter T timer unit T1 Duration of the pulse wave T _SN Pulse duration of a natural neural, electrical signal U circumferentially UH Clock V connecting structure ZF Time window ZS time signal ZV, ZV * time offset

Claims (40)

1. An implantable device for the location-selective recording of neuronal electrical signals propagating along at least one nerve fibre contained in a nerve fibre bundle, as well as for the selective electrical stimulation of the at least one nerve fibre, comprising the following components:

   - implantable electrode arrangement (E) which is arranged on a biocompatible carrier substrate (1) which can be applied in a cuff-like manner around the nerve fibre bundle and which in the implanted state has, orientated towards the nerve fibre bundle, a straight cylindrical carrier substrate surface (1') on which a first electrode arrangement (2) for the location-selective recording of the neuronal electrical signals and selective electrical stimulation of the at least one nerve fibre, and on which a second electrode arrangement (12) for recording an ECG signal are arranged,

   - an evaluation/control unit (A/S), which can be or is connected in an electrically conducting manner to the implantable electrode arrangement (E), in which the location-selectively recorded, neuronal, electrical signals as well as the ECG signal are evaluated in a time-resolved manner in such a way that a neuronal time signal correlated to a physiological parameter, preferably blood pressure, can be derived,

   - a first comparator unit (K1), connected to the evaluation/control unit (A/S), in which a characteristic relative time offset between the ECG signal and neuronal time signal correlated with the physiological parameter can be determined,

   - a first function generator (F1), connected to the evaluation/control unit (A/S), which within a time window determined by the evaluation/control unit (A/S) on the basis of the relative time offset generates a stimulation signal, adapted in terms of phase and time amplitude to the derived neuronal time signal correlated to the physiological parameter and composed of a plurality n of individual pulses (EP) as well as

   - a first signal-current converter (SSW1) which is directly or indirectly connected to the first function generator (F1) and the first electrode device (2) and sends the stimulation signal for the selective electrical stimulation of the at least one nerve fibre to the first electrode device (2),

   wherein the evaluation/control unit (A/S), the first comparator unit (K1), the first function generator (F1) as well as the first signal-current converter (SSW1) are combined as an implantable module.
2. The implantable device according to claim 1,
   characterised in that at least one second comparator unit (K2) is connected to the evaluation/ control unit (A/S),
   in that the second comparator unit (K2) compares at least one signal level, which is assigned to the neuronal time signal correlated to the physiological parameter, with a reference signal and generates a difference level value, and
   in that at least on the basis of the difference level value the evaluation/control unit (A/S) determines at least temporal amplitude profile of the simulation signal.
3. The implantable device according to claim 1 or 2,
   characterised in that in the implanted state, on the straight cylindrical carrier substrate surface (1') orientated toward the nerve fibre bundle the implantable electrode arrangement (E) comprises a third electrode arrangement (7) for the inhibition of neuronal electrical signals propagating unidirectionally along the nerve fibre bundle.
4. The implantable device according to any one of claims 1 to 3,
   characterised in that the implantable module comprises an electrical energy store (ES) and/or an induction-based signal and energy supply unit (SES) which is at least electrically connected to the evaluation/control unit (A/S).
5. The implantable device according to any one of claims 1 to 4,
   characterised in that an acceleration sensor (BS) is integrated into the implantable module and/or an implantably designed acceleration module (BS') that is separate from the module is provided, and in that the acceleration sensor (BS, BS') generates acceleration information and is electrically connected to the evaluation/control unit (A/S).
6. The implantable device according to any one of claims 1 to 5,
   characterised in that the first function generator (F1) is able to produce individual pulses which are each composed of a polarising and a repolarising square pulse-shaped partial signal, and in that between the first function generator (F1) and the first signal-current converter (SSW1) a first modulator (M1) is connected which enlarges and smooths a signal flank course assigned to the square pulse-shaped repolarising partial signal time-wise with regard to the polarising partial signal and harmonises a signal strength associated with each of the two partial signals.
7. The implantable device according to any one of claims 3 to 6,
   characterised in that a second function generator (F2), connected to the evaluation/control unit (A/S), is provided, which in terms of time before and/or during the determined time window generates an electrical blocking signal and
   in that the second function generator (F2) is directly or indirectly connected to a second signal-current converter (SSW2) which supplies the electrical blocking signal to the third electrode arrangement (7).
8. The implantable device according to claim 7,
   characterised in that the second function generator (F2) is able to produce individual pulses which are each composed of a polarising and a repolarising square pulse-like partial signal and
   in that between the second function generator (F2) and the second signal-current converter (SSW2) a second modulator (M2) is connected which enlarges and smooths a signal flank course assigned to the square pulse-shaped repolarising partial signal time-wise with regard to the polarising partial signal and harmonises a signal strength associated with each of the two partial signals.
9. The implantable device according to claim 8,
   characterised in that the second function generator (F2) as well as the second module (M2) are integrated into the implantable module.
10. The implantable device according to claim 6 or 8,
    characterised in that the first or second modulator (M1, M2) is designed in such a way that for each individual impulse the polarising partial signal can be separated from the repolarising partial signal by a zero signal level which can be produced by the first modulator (M1).
11. The implantable device according to any one of claims 1 to 10,
    characterised in that an electrode impedance measuring unit (EM) is part of the implantable module or is arranged on the carrier substrate (1) and connected to the electrode arrangement (E) as well as to the evaluation/control unit (A/S) and in that between each of the n individual pulses the electrode impedance unit (EM) performs an impedance measurement at least on electrodes of the first electrode arrangement (2).
12. The implantable device according to claim 11, characterised in that an electrical depolarisation device (EE) is part of the implantable module or is arranged on the carrier substrate (1) and is connected to the electrode arrangement (E) as well as to the evaluation/control unit (A/S) and
    in that in the event of residual polarisation on individual electrodes detected by the electrode impedance measuring unit (EM) the depolarisation device (EE) selectively depolarises these by means of applying electrical signals.
13. The implantable device according to any one of claims 4 to 12,
    characterised in that a separate blood pressure measuring system (SB) is provided which records absolute blood pressure values which can be supplied via the induction-based signal and energy supply unit (SES) to the evaluation/control unit (A/S) and in that on the basis of the absolute blood pressure values, the ECG signal, the neuronal time signal correlated with the physiological parameter as well as at least one reference signal, the evaluation/control unit (A/S) actuates the first function generator (F1) to generate the stimulation signal.
14. The implantable device according to claim 2, 5 and 13,
    characterised in that a storage unit, preferably in the form of a look-up table, is provided which is part of the evaluation/control unit (A/S) or is connected thereto as a separate unit,
    in that in the storage unit at least one following pieces of information can be stored and called up;
    differential level value, acceleration information, recorded absolute blood pressure.
15. The implantable device according to any one of claims 1 to 14,
    characterised in that the straight cylindrical carrier substrate surface (1') orientated towards the nerve fibre bundle has an axial (a) as well as circumferentially (U) orientated first extent and on which the first electrode arrangement (2) is applied, which

    - in axial sequence comprises at least three first electrode structures (3) each with at least two first electrode surfaces (4) arranged in the circumferential direction as well as

    - at least two axially spaced first electrode strips (5) extending in the circumferential direction and each assuming an annular shape and which axially encompass the at least three electrode structures on both sides and is connected or connectable to the evaluation/control unit (A/S).
16. The implantable device according to claim 15 as well as any one of claims 3 to 14,
    characterised in that the third electrode arrangement (7) is arranged in axial sequence on the straight-cylindrical support carrier surface (1') facing the nerve fibre bundle axially next to the first electrode arrangement (2) and comprises at least two axially spaced third electrode strips (8) extending in the circumferential direction (U) and each assuming an annular shape as well as
    axially between the at least two third electrode strips (8) at least one third electrode structure (13), in each case comprising at least two third electrode surfaces (9) arranged evenly distributed in the circumferential direction.
17. The implantable device according to claim 15 and 16,
    characterised in that the first and third electrode surfaces (4, 9) are arranged evenly distributed in the circumferential direction (U), each along a virtual circular line.
18. The implantable device according to claim 15 and 16,
    characterised in that the first and third electrode surfaces (4, 9) each have an axial (4a, 9a) extent orientated in the circumferential direction (4U, 9U),
    in that the extents (4a, 4U) of the first electrode surfaces (4) are identical in each case,
    in that the extents (9a, 9U) of the third electrode surfaces (9) are identical in each case and
    in that the extent (9U) of the third electrode surfaces (9) orientated in the circumferential direction is greater than the extent (4U) of the first electrode surfaces (4) orientated in the circumferential direction.
19. The implantable device according to claim 18,
    characterised in that the axial extents (4a, 4U) of the first and third electrode surfaces (4, 9) are identical.
20. The implantable device according to an one of claims 16 to 19,
    characterised in that the carrier substrate surface (1') on which the first and the third electrode arrangements (2, 7) is applied, is designed contiguously in one piece, i.e. without breaks.
21. The implantable device according to any one of claims 16 to 20,
    characterised in that the axial distance between the first electrode strips (5) is selected to be greater than or equal to the axial distance between the third electrode strips (8) and
    in that the axial distance between the third electrode strips measures between 0.5 cm and 3 cm, preferably between 0.75 cm and 1.25 cm.
22. The implantable device according to any one of claims 16 to 21,
    characterised in that the shape and size of the first and the third electrode strips (5, 8) are identical,
    in that the surface size of respectively the first and the third electrode surface (4, 9) are smaller than the surface size of respectively the first and third electrode strips (5, 8), preferably smaller than one quarter of the surface size of the first or third electrode strips (5, 8).
23. The implantable device according to any one of claims 16 to 22,
    characterised in that the first electrode surfaces (4) are made of a metallic material, preferably iridium oxide, which has a higher charge transfer capacity than a material of which the third electrode surfaces (9) consist.
24. The implantable device according to claim 23,
    characterised in that the metallic material of the first electrode surfaces (4) is iridium oxide and/or
    in that the material of the third electrode surfaces (9) is a metallic material, preferably platinum, or an electrically conductive polymer.
25. The implantable device according to any one of claims 16 to 24,
    characterised in that the first and the third electrode device (2, 7) can in each case be operated as a tripolar electrode arrangement, i.e. the first and the third electrode strips can in each case be polarised to the opposite polarity of the first and third electrode structure (3, 13).
26. The implantable device according to any one of claims 16 to 25,
    characterised in that the first electrode arrangement (7) envisages at least one optical waveguide device (10) which comprises at least two separate optical waveguide openings (11) arranged distributed in the circumferential direction (U).
27. The implantable device according to claim 26, characterised in that the at least two separate optical waveguide openings (11) are arranged evenly distributed along a virtual circular line and
    in that the optical waveguide openings (11) each have an axial (11a) and a circumferentially (11U) orientated first extent, which correspond to the those extents (9a, 9U) of the second electrode surfaces (9).
28. The implantable device according to any one of claims 16 to 27,
    characterised in that the first electrode surfaces (4) as well as the first electrode strips (5) of the first electrode arrangement (2) as well as the third electrode surfaces (9) as well as the third electrode strips (8) of the third electrode arrangement (7) are each applied to the carrier substrate surface (1') so that they do not project beyond the carrier substrate surface (1').
29. The implantable device according to any one of claims 1 to 28,
    characterised in that the carrier substrate (1) is made of at least one biocompatible polymer and at least in parts on the straight cylindrical carrier substrate surface (1') facing the nerve fibre bundle has an active substance that inhibits inflammatory reactions.
30. The implantable device according to any one of claims 1 to 29,
    characterised in that the carrier substrate (1) contains biocompatible polymer.
31. The implantable device according to claim 30 as well as claim 16,
    characterised in that the first and/or the third electrode strip (5, 8) each have at least one local opening and in that the first and/or the third electrode strips (5, 8) are connected flat with the carrier substrate surface (1') in such a way that the polymer at least partially penetrates the at least one opening.
32. The implantable device according to at least one of claims 1 to 31,
    characterised in that on the rear side of the carrier substrate surface (1') on the carrier substrate (1) at least two reference electrode surfaces (12) are applied.
33. The implantable device according to any one of claims 1 to 32,
    characterised in that in the area of the straight cylindrical carrier substrate surface (1') facing the nerve fibre bundle the biocompatible carrier substrate (1) has axially opposite marginal areas (14) at which the carrier substrate (1) has a greater substrate thickness than in the remaining carrier substrate area and
    in that the marginal areas (14) have rounded marginal edges.
34. The implantable device according to any one of claims 1 to 33,
    characterised in that in a carrier substrate area which cannot be applied in a cuff-like manner about the nerve fibre bundle, the biocompatible carrier substrate (1) has at least one opening (15) fully penetrating the carrier substrate.
35. The implantable device according to claim 34,
    characterised in that the at least one opening (15) is at least in parts enveloped with a metallic material.
36. The implantable device according to claim 16 and 30,
    characterised in that the first and/or the third electrode strips (5, 8) each have a metallic electrode strip substrate with a flat upper and lower side with at least one structural element locally projecting beyond the upper side in an orthogonal manner,
    in that the flat upper surface of the metallic electrode strip substrate is orientated in parallel to the carrier substrate surface and
    in that the electrode strip substrate is fully surrounded by the biocompatible polymer with the exception of a surface area of the at least one structural element which is orientated toward the carrier substrate surface and does not project beyond it.
37. The implantable device according to claim 36,
    characterised in that at least between the lower side of the electrode strip substrate and the biocompatible polymer of the carrier substrate an adhesion promoter layer or adhesion promotor layer device is introduced.
38. The implantable device according to claim 36 or 37, characterised in that the one surface area of the at least one structural element or a plane assigned to the surface area is orientated in parallel to the carrier substrate surface, in that the surface area is arranged in a freely accessible manner from the sides of the carrier substrate surface and in that the at least one structural element is connected in one piece to the electrode strip substrate.
39. The implantable device according to any one of claims 36 to 38,
    characterised in that a plurality of geometrically evenly distributed and identically designed structural elements is provided on the upper side of the metallic electrode strip substrate.
40. The implantable device according to any one of claims 36 to 39,
    characterised in that the at least one structural element is designed in a column, rib, sleeve or web-like manner.

Images